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1.
Pain Res Manag ; 2020: 3939757, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32676135

RESUMO

Aim: Orofacial chronic neuropathic pain commonly occurs following trigeminal nerve injuries. We investigated whether swimming exercise can reduce trigeminal neuropathic pain through improving antioxidant capacity. Materials and Methods: Twenty-eight Wistar rats of either sex and 180-220 grams were divided into 4 groups as sham, neuropathy, neuropathy + single bout exercise, and neuropathy + 2 weeks of exercise. Trigeminal neuropathy was carried out through chronic constriction injury (CCI) of infraorbital nerve. Protocols of exercise were included a single bout session (45 minutes) and a 2-week (45 minutes/day/6 days a week) swimming exercise. Mechanical allodynia was detected using Von Frey filaments. The activity of the serum antioxidant enzymes glutathione peroxidase and superoxides dismutase was assayed using ELISA kits. Results: We found that CCI significantly reduced facial pain threshold in both sexes (P < 0.05). Both swimming exercise protocols significantly reduced mechanical allodynia in female rats compared to the sham group; however, only 2 weeks of exercise were significantly effective in male rats. The activity of antioxidant enzyme glutathione peroxidase significantly (P < 0.05) decreased following CCI in female rats against that in the sham group and 2-week exercise significantly (P < 0.05) increased it toward the control level. The levels of glutathione peroxidase in male rats and superoxidase dismutase in both sexes were not significantly different compared to their sham groups. Conclusion: Swimming exercise alleviates trigeminal neuropathic pain in both sexes. Oxidative stress as a possible mechanism was involved in the effect of exercise on female rat trigeminal neuropathy.


Assuntos
Condicionamento Físico Animal/métodos , Caracteres Sexuais , Neuralgia do Trigêmeo , Animais , Modelos Animais de Doenças , Feminino , Hiperalgesia , Masculino , Estresse Oxidativo/fisiologia , Limiar da Dor/fisiologia , Ratos , Ratos Wistar , Neuralgia do Trigêmeo/metabolismo
2.
Am J Physiol Regul Integr Comp Physiol ; 319(3): R366-R375, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32726157

RESUMO

We have tested the feasibility of thermal grills, a harmless method to induce pain. The thermal grills consist of interlaced tubes that are set at cool or warm temperatures, creating a painful "illusion" (no tissue injury is caused) in the brain when the cool and warm stimuli are presented collectively. Advancement in objective pain assessment research is limited because the gold standard, the self-reporting pain scale, is highly subjective and only works for alert and cooperative patients. However, the main difficulty for pain studies is the potential harm caused to participants. We have recruited 23 subjects in whom we induced electric pulses and thermal grill (TG) stimulation. The TG effectively induced three different levels of pain, as evidenced by the visual analog scale (VAS) provided by the subjects after each stimulus. Furthermore, objective physiological measurements based on electrodermal activity showed a significant increase in levels as stimulation level increased. We found that VAS was highly correlated with the TG stimulation level. The TG stimulation safely elicited pain levels up to 9 out of 10. The TG stimulation allows for extending studies of pain to ranges of pain in which other stimuli are harmful.


Assuntos
Resposta Galvânica da Pele/fisiologia , Temperatura Alta , Limiar da Dor/fisiologia , Dor/fisiopatologia , Sensação Térmica/fisiologia , Adulto , Temperatura Baixa , Feminino , Voluntários Saudáveis , Humanos , Medição da Dor/métodos
3.
PLoS One ; 15(5): e0232108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32379766

RESUMO

Influential theoretical accounts take the position that classical conditioning can induce placebo effects through conscious expectancies. In the current study two different conditioning procedures (hidden and open) were used to separate expectancy from conditioning in order to reveal the role of expectancy in the formation of nocebo hyperalgesia. Eighty-seven healthy females were randomly assigned to three groups (hidden conditioning, open conditioning, and control). Participants were selected according to the Fear of Pain Questionnaire scores and assigned to two subgroups: high and low level of fear of pain (trait). They received electrocutaneous pain stimuli preceded by either an orange or blue color. During the conditioning phase, one color was paired with pain stimuli of moderate intensity (control stimuli) and the other color was paired with pain stimuli of high intensity (nocebo stimuli) in both hidden and open conditioning groups. Only participants in the open conditioning group were informed about this association, however just before the testing phase the expectancy of hyperalgesia induced in this way was withdrawn. In the control group, both colors were followed by control pain stimuli. During the testing phase all participants received a series of stimuli of the same intensity, regardless of the preceding color. Participants rated pain intensity, expectancy of pain intensity and fear (state). We found that nocebo hyperalgesia was induced by hidden rather than open conditioning. The hidden conditioning procedure did not produce conscious expectancies related to pain. Nocebo hyperalgesia was induced in participants with low and high fear of pain and there was no difference in the magnitude of the nocebo effect between both groups. Nocebo hyperalgesia was not predicted by the fear of upcoming painful stimuli.


Assuntos
Condicionamento Clássico/fisiologia , Hiperalgesia/fisiopatologia , Efeito Nocebo , Adulto , Medo/fisiologia , Medo/psicologia , Feminino , Humanos , Motivação/fisiologia , Dor/fisiopatologia , Dor/psicologia , Medição da Dor/métodos , Medição da Dor/psicologia , Limiar da Dor/fisiologia , Limiar da Dor/psicologia
4.
Pain Pract ; 20(6): 676-694, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32255268

RESUMO

BACKGROUND: Exercise, a cornerstone in current treatments for people with musculoskeletal pain, elicits a phenomenon called exercise-induced hypoalgesia (EIH), which may result in reduced pain intensity and/or increased pain thresholds. However, EIH can be impaired in patients with musculoskeletal pain, and psychosocial factors may play a mediating role in EIH. OBJECTIVE: The aim of this study was to systematically review the scientific literature regarding the association between psychosocial factors and EIH in healthy people and people with musculoskeletal pain. METHODS: An extensive search in databases including Medline Ovid, Embase, Web of Science, PsycINFO Ovid, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCOhost was carried out. Two reviewers independently carried out study selection, data extraction, and critical appraisal. Included studies analyzed the association or effect of psychosocial factors on EIH in adults with or without musculoskeletal pain. RESULTS: Nine cross-sectional studies were included, 6 involving healthy people and 4 involving people with musculoskeletal pain; 1 study included both. Overall risk of bias was high. Different types of exercise bouts, psychosocial factors, and/or outcome measures were used across studies. In healthy people and people with musculoskeletal pain, most studies did not find an association between psychosocial factors and EIH. However, 1 study involving musculoskeletal pain and 2 studies with healthy people did find a significant association. CONCLUSION: Due to poor quality and heterogeneity between studies, no conclusions can be drawn regarding whether psychosocial factors are associated with EIH or not. This review includes recommendations and directions for further research to investigate the role of psychosocial factors on EIH.


Assuntos
Exercício Físico/psicologia , Dor Musculoesquelética/psicologia , Dor Musculoesquelética/reabilitação , Limiar da Dor/fisiologia , Limiar da Dor/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Dor Musculoesquelética/fisiopatologia , Percepção da Dor/fisiologia , Adulto Jovem
5.
J Appl Oral Sci ; 28: e20190407, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32236355

RESUMO

INTRODUCTION: This study aimed to evaluate whether the presence of awake bruxism was associated with temporomandibular dysfunction symptoms, pain threshold at pressure, pain vigilance, oral health-related quality of life (OHRQoL), and anxiety and depression symptoms in patients undergoing orthodontic treatment. METHODOLOGY: This observational study followed patients who had started receiving orthodontic treatment for six months. The following variables were measured three times (at baseline, one month, and six months): pressure pain threshold (PPT) in the right and left masseter, anterior temporalis, and temporomandibular joint (TMJ), and right forearm; pain vigilance and awareness questionnaire; and shortened form of the oral health impact profile (OHIP-14). Anxiety and depression symptoms were measured using the Beck anxiety inventory and the Beck depression inventory, respectively. The patients were divided into two main groups according to the presence (n=56) and absence (n=58) of possible awake bruxism. The multi-way analysis of variance (ANOVA) was applied on the date (p=0.050). RESULTS: TMJ and/or muscle pain were not observed in both groups. Time, sex, age group, and awake bruxism did not affect the PPT in the masticatory muscles and pain vigilance (p>0.050). However, the primary effect of awake bruxism was observed when anxiety (ANOVA: F=8.61, p=0.004) and depression (ANOVA: F=6.48, p=0.012) levels were higher and the OHRQoL was lower (ANOVA: F=8.61, p=0.004). CONCLUSION: The patients with self-reported awake bruxism undergoing an orthodontic treatment did not develop TMJ/masticatory muscle pain. The self-reported awake bruxism is associated with higher anxiety and depression levels and a poorer OHRQoL in patients during the orthodontic treatment.


Assuntos
Ansiedade/fisiopatologia , Bruxismo/psicologia , Bruxismo/terapia , Depressão/fisiopatologia , Limiar da Dor/psicologia , Qualidade de Vida/psicologia , Autorrelato , Adolescente , Adulto , Análise de Variância , Bruxismo/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mialgia , Limiar da Dor/fisiologia , Escalas de Graduação Psiquiátrica , Psicometria , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Transtornos da Articulação Temporomandibular/fisiopatologia , Transtornos da Articulação Temporomandibular/psicologia , Adulto Jovem
6.
Proc Natl Acad Sci U S A ; 117(18): 10045-10054, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32312820

RESUMO

Although pain is a prevalent nonmotor symptom in Parkinson's disease (PD), it is undertreated, in part because of our limited understanding of the underlying mechanisms. Considering that the basal ganglia are implicated in pain sensation, and that their synaptic outputs are controlled by the subthalamic nucleus (STN), we hypothesized that the STN might play a critical role in parkinsonian pain hypersensitivity. To test this hypothesis, we established a unilateral parkinsonian mouse model with moderate lesions of dopaminergic neurons in the substantia nigra. The mice displayed pain hypersensitivity and neuronal hyperactivity in the ipsilesional STN and in central pain-processing nuclei. Optogenetic inhibition of STN neurons reversed pain hypersensitivity phenotypes in parkinsonian mice, while hyperactivity in the STN was sufficient to induce pain hypersensitivity in control mice. We further demonstrated that the STN differentially regulates thermal and mechanical pain thresholds through its projections to the substantia nigra pars reticulata (SNr) and the internal segment of the globus pallidus (GPi)/ventral pallidum (VP), respectively. Interestingly, optogenetic inhibition of STN-GPi/STN-VP and STN-SNr projections differentially elevated mechanical and thermal pain thresholds in parkinsonian mice. In summary, our results support the hypothesis that the STN and its divergent projections play critical roles in modulating pain processing under both physiological and parkinsonian conditions, and suggest that inhibition of individual STN projections may be a therapeutic strategy to relieve distinct pain phenotypes in PD.


Assuntos
Neurônios/fisiologia , Dor/fisiopatologia , Doença de Parkinson/fisiopatologia , Núcleo Subtalâmico/fisiopatologia , Animais , Gânglios da Base/efeitos dos fármacos , Gânglios da Base/fisiopatologia , Modelos Animais de Doenças , Antagonistas de Dopamina/farmacologia , Globo Pálido/efeitos dos fármacos , Humanos , Hipersensibilidade , Camundongos , Neurônios/efeitos dos fármacos , Oxidopamina/farmacologia , Dor/complicações , Limiar da Dor/efeitos dos fármacos , Limiar da Dor/fisiologia , Doença de Parkinson/complicações , Substância Negra/fisiopatologia , Núcleo Subtalâmico/efeitos dos fármacos
7.
J Neurosci ; 40(18): 3517-3532, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32245829

RESUMO

One of the first signs of viral infection is body-wide aches and pain. Although this type of pain usually subsides, at the extreme, viral infections can induce painful neuropathies that can last for decades. Neither of these types of pain sensitization is well understood. A key part of the response to viral infection is production of interferons (IFNs), which then activate their specific receptors (IFNRs) resulting in downstream activation of cellular signaling and a variety of physiological responses. We sought to understand how type I IFNs (IFN-α and IFN-ß) might act directly on nociceptors in the dorsal root ganglion (DRG) to cause pain sensitization. We demonstrate that type I IFNRs are expressed in small/medium DRG neurons and that their activation produces neuronal hyper-excitability and mechanical pain in mice. Type I IFNs stimulate JAK/STAT signaling in DRG neurons but this does not apparently result in PKR-eIF2α activation that normally induces an anti-viral response by limiting mRNA translation. Rather, type I IFNs stimulate MNK-mediated eIF4E phosphorylation in DRG neurons to promote pain hypersensitivity. Endogenous release of type I IFNs with the double-stranded RNA mimetic poly(I:C) likewise produces pain hypersensitivity that is blunted in mice lacking MNK-eIF4E signaling. Our findings reveal mechanisms through which type I IFNs cause nociceptor sensitization with implications for understanding how viral infections promote pain and can lead to neuropathies.SIGNIFICANCE STATEMENT It is increasingly understood that pathogens interact with nociceptors to alert organisms to infection as well as to mount early host defenses. Although specific mechanisms have been discovered for diverse bacterial and fungal pathogens, mechanisms engaged by viruses have remained elusive. Here we show that type I interferons, one of the first mediators produced by viral infection, act directly on nociceptors to produce pain sensitization. Type I interferons act via a specific signaling pathway (MNK-eIF4E signaling), which is known to produce nociceptor sensitization in inflammatory and neuropathic pain conditions. Our work reveals a mechanism through which viral infections cause heightened pain sensitivity.


Assuntos
Viroses do Sistema Nervoso Central/metabolismo , Interferon Tipo I/toxicidade , Nociceptores/metabolismo , Limiar da Dor/fisiologia , Dor/metabolismo , Doenças do Sistema Nervoso Periférico/metabolismo , Animais , Células Cultivadas , Viroses do Sistema Nervoso Central/induzido quimicamente , Viroses do Sistema Nervoso Central/patologia , Feminino , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Nociceptores/efeitos dos fármacos , Nociceptores/patologia , Dor/induzido quimicamente , Dor/patologia , Limiar da Dor/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/patologia
8.
Pain Physician ; 23(2): 219-227, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32214304

RESUMO

BACKGROUND: A method for assessing dynamic muscle hyperalgesia (dynamic pressure algometry) has been developed and applied in tension-type and migraine headaches. OBJECTIVES: To investigate differences in dynamic pressure pain assessment over the trigeminal area between men with cluster headache (CH) and headache-free controls, and the association between dynamic and static pressure pain sensitivity. STUDY DESIGN: A case-control study. SETTING: Tertiary urban hospital. METHODS: Forty men with episodic CH and 40 matched controls participated. Dynamic pressure pain sensitivity was assessed with a dynamic pressure algometry set consisting of 8 rollers with different fixed levels (500, 700, 850, 1,350, 1,550, 2,200, 3,850, and 5,300 g). Each roller was moved at a speed of 0.5 cm/sec over a diagonal line covering the temporalis muscle from an anterior to posterior direction. The dynamic pressure threshold (DPT; load level of the first painful roller) and the pain intensity perceived at the DPT level (roller-evoked pain) were assessed. Static pressure pain thresholds (PPT) were also assessed with a digital pressure algometer applied statically over the mid-muscle belly of the temporalis. Patients were assessed in a remission phase, at least 3 months from the last cluster attack, and without preventive medication. RESULTS: Side-to-side consistency between DPTs (r = 0.781, P < 0.001), roller-evoked pain on DPT (r = 0.586; P < 0.001), and PPTs (r = 0.874; P < 0.001) were found in men with CH. DPT was moderately, bilaterally, and side-to-side associated with PPTs (0.663 > r > 0.793, all P < 0.001). Men with CH had bilateral lower DPT and PPT and reported higher levels of roller-evoked pain (all P < 0.001) than headache-free controls. LIMITATIONS: Only men with episodic CH were included. CONCLUSIONS: This study supports that a dynamic pressure algometry is as valid as a static pressure algometry for assessing pressure pain sensitivity in patients with CH. Assessing both dynamic and static pain sensitivity may provide new opportunities for differentiated diagnostics. KEY WORDS: Cluster headache, dynamic pressure pain, pressure pain threshold.


Assuntos
Cefaleia Histamínica/diagnóstico , Hiperalgesia/diagnóstico , Medição da Dor/métodos , Dor/diagnóstico , Pressão/efeitos adversos , Músculo Temporal/patologia , Adulto , Estudos de Casos e Controles , Cefaleia Histamínica/complicações , Humanos , Hiperalgesia/etiologia , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Limiar da Dor/fisiologia
9.
PLoS One ; 15(3): e0230315, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32182261

RESUMO

Humans do not respond to the pain of all humans equally; physical appearance and associated group identity affect how people respond to the pain of others. Here we ask if a similar differential response occurs when humans evaluate different individuals of another species. Beliefs about pain in pet dogs (Canis familiaris) provide a powerful test, since dogs vary so much in size, shape, and color, and are often associated with behavioral stereotypes. Using an on-line survey, we asked both the general public and veterinarians to rate pain sensitivity in 28 different dog breeds, identified only by their pictures. We found that both the general public and veterinarians rated smaller dogs (i.e. based on height and weight) as being more sensitive to pain; the general public respondents rated breeds associated with breed specific legislation as having lower pain sensitivity. While there is currently no known physiological basis for such breed-level differences, over 90% of respondents from both groups indicated belief in differences in pain sensitivity among dog breeds. We discuss how these results inform theories of human social discrimination and suggest that the perception of breed-level differences in pain sensitivity may affect the recognition and management of painful conditions in dogs.


Assuntos
Cães/fisiologia , Limiar da Dor/fisiologia , Dor/veterinária , Animais , Competência Clínica , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Dor/diagnóstico , Manejo da Dor , Especificidade da Espécie , Inquéritos e Questionários/estatística & dados numéricos , Médicos Veterinários/estatística & dados numéricos
10.
J Neurosci ; 40(17): 3424-3442, 2020 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-32217613

RESUMO

The parabrachial (PB) complex mediates both ascending nociceptive signaling and descending pain modulatory information in the affective/emotional pain pathway. We have recently reported that chronic pain is associated with amplified activity of PB neurons in a rat model of neuropathic pain. Here we demonstrate that similar activity amplification occurs in mice, and that this is related to suppressed inhibition to lateral parabrachial (LPB) neurons from the CeA in animals of either sex. Animals with pain after chronic constriction injury of the infraorbital nerve (CCI-Pain) displayed higher spontaneous and evoked activity in PB neurons, and a dramatic increase in after-discharges, responses that far outlast the stimulus, compared with controls. LPB neurons in CCI-Pain animals showed a reduction in inhibitory, GABAergic inputs. We show that, in both rats and mice, LPB contains few GABAergic neurons, and that most of its GABAergic inputs arise from CeA. These CeA GABA neurons express dynorphin, somatostatin, and/or corticotropin releasing hormone. We find that the efficacy of this CeA-LPB pathway is suppressed in chronic pain. Further, optogenetically stimulating this pathway suppresses acute pain, and inhibiting it, in naive animals, evokes pain behaviors. These findings demonstrate that the CeA-LPB pathway is critically involved in pain regulation, and in the pathogenesis of chronic pain.SIGNIFICANCE STATEMENT We describe a novel pathway, consisting of inhibition by dynorphin, somatostatin, and corticotropin-releasing hormone-expressing neurons in the CeA that project to the parabrachial nucleus. We show that this pathway regulates the activity of pain-related neurons in parabrachial nucleus, and that, in chronic pain, this inhibitory pathway is suppressed, and that this suppression is causally related to pain perception. We propose that this amygdalo-parabrachial pathway is a key regulator of both chronic and acute pain, and a novel target for pain relief.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Dor Crônica/fisiopatologia , Neuralgia/fisiopatologia , Percepção da Dor/fisiologia , Núcleos Parabraquiais/fisiopatologia , Potenciais de Ação/fisiologia , Animais , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Vias Neurais/fisiopatologia , Neurônios/fisiologia , Medição da Dor , Limiar da Dor/fisiologia
11.
Psychopharmacology (Berl) ; 237(5): 1545-1555, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32114633

RESUMO

RATIONALE: Over the last decade, oxycodone has become one of the most widely abused drugs in the USA. Oxycodone use disorder (OUD) is a serious health problem that has prompted a need to develop animal models of OUD that have both face and predictive validity. Oxycodone use in humans is more prevalent in women and leads to pronounced hyperalgesia and irritability during withdrawal. However, unclear is whether current animal models of oxycodone self-administration recapitulate these characteristics in humans. OBJECTIVES: We assessed the face validity of a model of extended-access oxycodone self-administration in rats by examining the escalation of oxycodone intake and behavioral symptoms of withdrawal, including irritability-like behavior and mechanical nociception, in male and female Wistar rats. RESULTS: Both male and female rats escalated their oxycodone intake over fourteen 12-h self-administration sessions. After escalation, female rats administered more drug than male rats. No differences in plasma oxycodone levels were identified, but males had a significantly higher level of oxycodone in the brain at 30 min. Extended access to oxycodone significantly decreased aggressive-like behavior and increased defensive-like behaviors when tested immediately after a 12-h self-administration session, followed by a rebound increase in aggressive-like behavior 12 h into withdrawal. Tests of mechanical nociception thresholds during withdrawal indicated pronounced hyperalgesia. No sex differences in irritability-like behavior or pain sensitivity were observed. CONCLUSIONS: The present study demonstrated the face validity of the extended access model of oxycodone self-administration by identifying sex differences in the escalation of oxycodone intake and pronounced changes in pain and affective states.


Assuntos
Analgésicos Opioides/administração & dosagem , Oxicodona/administração & dosagem , Limiar da Dor/efeitos dos fármacos , Limiar da Dor/psicologia , Caracteres Sexuais , Síndrome de Abstinência a Substâncias/psicologia , Analgésicos Opioides/efeitos adversos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Emoções/efeitos dos fármacos , Emoções/fisiologia , Feminino , Masculino , Oxicodona/efeitos adversos , Limiar da Dor/fisiologia , Ratos , Ratos Wistar , Autoadministração , Síndrome de Abstinência a Substâncias/metabolismo
12.
Curr Pain Headache Rep ; 24(4): 11, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32072357

RESUMO

PURPOSE OF REVIEW: This review aims to identify perioperative patient-related factors that are associated with the development of persistent postoperative pain (PPP) in patients undergoing spine surgery. RECENT FINDINGS: Twenty-one studies published between 2000 and 2019 were included in this literature review. The following five patient-related factors were identified to be associated with the development of PPP after spine surgery: anxiety, depression, pain catastrophizing, pain sensitivity, and preoperative opioid consumption. The existing literature suggests that the risk factors for developing chronic pain after spine surgery appear to be similar to those for other types of surgery. Psychological factors and preoperative opioid consumption are associated with developing chronic pain after spinal surgery. Other factors such as gender, age, preoperative pain intensity, and immediate postoperative pain may also be involved but the evidence on this is limited.


Assuntos
Procedimentos Ortopédicos/efeitos adversos , Dor Pós-Operatória/etiologia , Coluna Vertebral/cirurgia , Ansiedade/complicações , Catastrofização/complicações , Dor Crônica/etiologia , Depressão/complicações , Feminino , Humanos , Masculino , Limiar da Dor/fisiologia , Dor Pós-Operatória/psicologia , Fatores de Risco , Fatores Sexuais
13.
BMC Neurol ; 20(1): 43, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32007103

RESUMO

BACKGROUND: Pharmacological treatment of patients with tension-type headache (TTH) includes symptomatic (acute) and prophylactic (preventive) medication. No previous study has investigated variables associated to symptomatic medication intake in TTH. Our aim was to assess the association of clinical, psychological and neurophysiological outcomes with the use and timing of the use of symptomatic medication in TTH. METHODS: A longitudinal observational study was conducted. One hundred and sixty-eight (n = 168) patients with TTH participated. Pain features of the headache (intensity, frequency, duration), burden of headache (Headache Disability Inventory), sleep quality (Pittsburgh Sleep Quality Index), anxiety/depression (Hospital Anxiety and Depression Scale), trait/state anxiety levels (State-Trait Anxiety Inventory), and bilateral pressure pain thresholds on the temporalis, C5-C6 joint, second metacarpal and tibialis anterior were assessed. Symptomatic medication intake was also collected for a 6-months follow-up period. Differences between patients using or not using symptomatic medication, depending on self-perceived effectiveness, and time (early during an attack, i.e., the first 5 min, or when headache attack is intense) when the symptomatic medication was taken were calculated. RESULTS: One hundred and thirty-six (n = 136, 80%) reported symptomatic medication intake for headache (73% NSAIDs). Sixteen (12%) reported no pain relief, 81 (59%) experienced moderate relief and 39 (29%) total pain relief. Fifty-eight (43%) took 'early medication' whereas 78 (57%) took 'late medication'. Patients taking symptomatic medication in general showed lower headache frequency and lower depressive levels than those patients not taking medication. Symptomatic medication was more effective in patients with lower headache history, frequency, and duration, and lower emotional burden. No differences in pressure pain sensitivity were found depending on the self-perceived effectiveness of medication. Patients taking 'late symptomatic' medication exhibited more widespread pressure pain sensitivity than those taking 'early medication'. CONCLUSIONS: This study found that the effectiveness of symptomatic medication was associated with better headache parameters (history, frequency, or duration) and lower emotional burden. Further, consuming early symptomatic medication at the beginning of a headache attack (the first 5 min) could limit widespread pressure pain sensitivity.


Assuntos
Analgésicos/uso terapêutico , Cefaleia do Tipo Tensional/tratamento farmacológico , Adulto , Europa (Continente) , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Limiar da Dor/fisiologia
14.
Muscle Nerve ; 61(5): 653-656, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32052453

RESUMO

INTRODUCTION: Assessment of sensory impairment in diabetic patients by pain threshold test using intraepidermal electrical stimulation (IES) is a recently developed technique. However, there are no normative pain thresholds in healthy people. METHODS: We examined pain, vibration, and pressure thresholds in 178 healthy subjects using IES, vibration perception testing (VPT), and Semmes-Weinstein monofilament testing (SWMT). RESULTS: The mean values for each age group for pain threshold ranged from 0.07 to 0.12 mA. Pain thresholds were unaffected by age. As the age increased, VPT values decreased from 18.0 to 10.6 seconds and SWMT values increased from 21.4 to 45.3 g/mm2 . There were no significant differences in pain threshold, VPT, and SWMT between men and women. DISCUSSION: The pain threshold test appears to be useful for diabetic neuropathy screening because normative values are not affected by age.


Assuntos
Envelhecimento/fisiologia , Neuropatias Diabéticas/diagnóstico , Limiar da Dor/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Neuropatias Diabéticas/fisiopatologia , Estimulação Elétrica , Feminino , Voluntários Saudáveis , Humanos , Japão , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Percepção do Tato , Vibração , Adulto Jovem
15.
Muscle Nerve ; 61(5): 662-670, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32083755

RESUMO

INTRODUCTION: We investigated the mechanisms underlying immobilization-induced muscle pain in rats. METHODS: In rat skeletal muscle, pressure pain threshold (PPT) of the gastrocnemius muscle was measured, and nerve growth factor (NGF) level, peripheral nerve fiber density, macrophage number, and interleukin-1ß (IL-1ß) mRNA expression were examined. An NGF receptor inhibitor was injected intramuscularly to assess the relationship between PPT and NGF levels. RESULTS: Immobilization resulted in a decrease in PPT and increases in NGF level, C-fiber density, M1 macrophage number, and IL-1ß mRNA expression. Injection of NGF receptor inhibitor reversed the decrease in PPT. DISCUSSION: NGF upregulation may be a major contributor to immobilization-induced muscle pain. The increases in C-fiber density, M1 macrophage number, and IL-1ß mRNA expression may be related to immobilization-induced muscle pain.


Assuntos
Hiperalgesia/metabolismo , Imobilização , Interleucina-1beta/genética , Macrófagos/patologia , Músculo Esquelético/metabolismo , Fator de Crescimento Neural/metabolismo , Limiar da Dor/fisiologia , RNA Mensageiro/metabolismo , Animais , Carbazóis/farmacologia , Moldes Cirúrgicos , Inibidores Enzimáticos/farmacologia , Membro Posterior , Hiperalgesia/patologia , Hiperalgesia/fisiopatologia , Alcaloides Indólicos/farmacologia , Masculino , Músculo Esquelético/inervação , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Fibras Nervosas/patologia , Fibras Nervosas Amielínicas/patologia , Limiar da Dor/efeitos dos fármacos , Pressão , Distribuição Aleatória , Ratos , Ratos Wistar , Receptor trkA/antagonistas & inibidores
16.
J Headache Pain ; 21(1): 16, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059650

RESUMO

BACKGROUND: People with migraine have localised (i.e., cephalic) mechanical sensitivity. There is uncertainty regarding widespread (i.e., extra-cephalic) mechanical sensitivity and variations in mechanical sensitivity throughout the migraine cycle. Therefore, this study aimed (1) to comprehensively assess mechanical sensitivity in both cephalic and extra-cephalic regions during the preictal, ictal, postictal and interictal phases; and (2) to compare these findings with mechanical sensitivity at corresponding time-points and locations in healthy participants. METHODS: According to sample size calculations, 19 people with migraine and 19 matched healthy volunteers participated in a prospective longitudinal study. Pressure pain thresholds were evaluated in three cephalic regions (temporalis, upper trapezius and C1 paraspinal muscles) and two extra-cephalic regions (extensor carpi radialis and tibialis anterior muscle) with a digital algometer during the four phases of the migraine cycle in people with migraine and at corresponding intervals and locations in healthy participants. Linear mixed model analyses with a random intercept were used. RESULTS: People with migraine had increased mechanical sensitivity in cephalic and extra-cephalic regions in all phases of the migraine cycle compared to healthy participants. Furthermore, this mechanical sensitivity was more severe in the preictal, ictal and postictal phase compared to the interictal phase in cephalic and extra-cephalic regions. CONCLUSION: People with migraine have localised as well as widespread mechanical sensitivity compared to healthy participants. This sensitivity is even more pronounced immediately before, during and after a migraine attack.


Assuntos
Transtornos de Enxaqueca/fisiopatologia , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Limiar da Dor/fisiologia , Estudos Prospectivos
17.
Exp Neurol ; 327: 113240, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32045596

RESUMO

The voltage sodium channel 1.8 (NaV1.8) in the dorsal root ganglion (DRG) neurons contributes to the initiation and development of chronic inflammatory and neuropathic pain. However, an effective intervention on NaV1.8 remains to be studied in pre-clinical research and clinical trials. In this study, we aimed to investigate whether transcription factor 4 (TCF4) overexpression represses NaV1.8 expression in DRG neurons, thus preventing the development of chronic pain. Using chromatin immunoprecipitation (CHIP), we verified the interaction of TCF4 and sodium voltage-gated channel alpha subunit 10A (SCN10A) enhancer in HEK293 cells and rat DRG neurons. Using a dual luciferase reporter assay, we confirmed the transcriptional inhibition of TCF4 on SCN10A promoter in vitro. To investigate the regulation of TCF4 on Nav1.8, we then upregulated TCF4 expression by intrathecally delivering an overexpression of recombinant adeno-associated virus (rAAV) in the Complete Freund's adjuvant (CFA)-induced inflammatory pain model and spared nerve injury (SNI)-induced neuropathic pain model. By using a quantitative polymerase chain reaction (qPCR), western blot, and immunostaining, we evaluated NaV1.8 expression after a noxious stimulation and the application of the TCF4 overexpression virus. We showed that the intrathecal delivery of TCF4 overexpression virus significantly repressed the increase of NaV1.8 and prevented the development of hyperalgesia in rats. Moreover, we confirmed the efficient role of an overexpressed TCF4 in preventing the CFA- and SNI-induced neuronal hyperexcitability by calcium imaging. Our results suggest that attenuating the dysregulation of NaV1.8 by targeting TCF4 may be a novel therapeutic strategy for chronic inflammatory and neuropathic pain.


Assuntos
Gânglios Espinais/metabolismo , Hiperalgesia/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.8/metabolismo , Neuralgia/metabolismo , Neurônios/metabolismo , Fator de Transcrição 4/metabolismo , Animais , Regulação para Baixo , Células HEK293 , Humanos , Hiperalgesia/genética , Inflamação/genética , Inflamação/metabolismo , Masculino , Canal de Sódio Disparado por Voltagem NAV1.8/genética , Neuralgia/genética , Limiar da Dor/fisiologia , Ratos , Ratos Sprague-Dawley , Fator de Transcrição 4/genética , Regulação para Cima
18.
Arthritis Rheumatol ; 72(6): 966-971, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31904188

RESUMO

OBJECTIVE: Pain sensitization contributes to the complex osteoarthritis (OA) pain experience. The relationship between imaging features of hand OA and clinically assessed pain sensitization is largely unexplored. This study was undertaken to examine the association of structural and inflammatory features of hand OA with local pressure pain thresholds (PPTs) in the Nor-Hand study. METHODS: The cross-sectional relationship of severity of structural radiographic features of hand OA (measured according to the Kellgren/Lawrence scale [grade 0-4] and the absence or presence of erosive joint disease) as well as ultrasound-detected hand joint inflammation (assessed by gray-scale synovitis [grade 0-3] and the absence or presence of power Doppler activity) to the PPTs of 2 finger joints was examined by multilevel regression analyses adjusted for age, sex, and body mass index, using beta values with 95% confidence intervals (95% CIs). RESULTS: A total of 570 joints in 285 participants included in the Nor-Hand study were assessed. Greater structural and inflammatory severity was associated with lower PPTs, with adjusted beta values of -0.5 (95% CI -0.6, -0.4) per Kellgren/Lawrence grade increase, -1.4 (95% CI -1.8, -0.9) for erosive versus non-erosive joints, -0.7 (95% CI -0.9, -0.6) per gray-scale synovitis grade increase, and -1.5 (95% CI -1.8, -1.1) for joints with power Doppler activity on ultrasound versus those without. CONCLUSION: Greater severity of structural pathologic features and hand joint inflammation was associated with lower PPTs in the finger joints of patients with hand OA, indicating pain sensitization. Our results indicate that pain sensitization might be driven by structural and inflammatory pathology in hand OA.


Assuntos
Artralgia/diagnóstico por imagem , Osteoartrite/diagnóstico por imagem , Limiar da Dor/fisiologia , Radiografia/estatística & dados numéricos , Ultrassonografia Doppler/estatística & dados numéricos , Idoso , Artralgia/etiologia , Artralgia/fisiopatologia , Sensibilização do Sistema Nervoso Central/fisiologia , Estudos Transversais , Feminino , Articulações dos Dedos/diagnóstico por imagem , Articulações dos Dedos/fisiopatologia , Articulação da Mão/diagnóstico por imagem , Articulação da Mão/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/complicações , Osteoartrite/fisiopatologia , Pressão
19.
J Neurosci ; 40(7): 1538-1548, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31896672

RESUMO

Our sensory impressions of pain are generally thought to represent the noxious properties of an agent but can be influenced by the predicted level of threat. Predictions can be sourced from higher-order cognitive processes, such as schemas, but the extent to which schemas can influence pain perception relative to bottom-up sensory inputs and the underlying neural underpinnings of such a phenomenon are unclear. Here, we investigate how threat predictions generated from learning a cognitive schema lead to inaccurate sensory impressions of the pain stimulus. Healthy male and female participants first detected a linear association between cue values and stimulus intensity and rated pain to reflect the linear schema when compared with uncued heat stimuli. The effect of bias on pain ratings was reduced when prediction errors (PEs) increased, but pain perception was only partially updated when measured against stepped increases in PEs. Cognitive, striatal, and sensory regions graded their responses to changes in predicted threat despite the PEs (p < 0.05, corrected). Individuals with more catastrophic thinking about pain and with low mindfulness were significantly more reliant on the schema than on the sensory evidence from the pain stimulus. These behavioral differences mapped to variability in responses of the striatum and ventromedial prefrontal cortex. Thus, this study demonstrates a significant role of higher-order schemas in pain perception and indicates that pain perception is biased more toward predictions and less toward nociceptive inputs in individuals who report less mindfulness and more fear of pain.SIGNIFICANCE STATEMENT This study demonstrates that threat predictions generated from cognitive schemas continue to influence pain perception despite increasing prediction errors arising in pain pathways. Individuals first formed a cognitive schema of linearity in the relationship between the cued threat value and the stimulus intensity. Subsequently, the linearity was reduced gradually, and participants partially updated their evaluations of pain in relation to the stepped increases in prediction errors. Individuals who continued to rate pain based more on the predicted threat than on changes in nociceptive inputs reported high pain catastrophizing and less mindful-awareness scores. These two affects mapped to activity in the ventral and dorsal striatum, respectively. These findings direct us to a significant role of top-down processes in pain perception.


Assuntos
Antecipação Psicológica/fisiologia , Encéfalo/fisiologia , Processos Mentais/fisiologia , Noxas , Percepção da Dor/fisiologia , Adulto , Mapeamento Encefálico , Catastrofização , Cognição/fisiologia , Corpo Estriado/fisiopatologia , Sinais (Psicologia) , Feminino , Temperatura Alta/efeitos adversos , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Medição da Dor , Limiar da Dor/fisiologia , Sensação/fisiologia , Córtex Somatossensorial/fisiopatologia , Adulto Jovem
20.
Exp Neurol ; 327: 113208, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31962127

RESUMO

Spinal cord injury (SCI) produces both locomotor deficits and sensory dysfunction that greatly reduce the overall quality of life. Mechanisms underlying chronic pain include increased neuro-inflammation and changes in spinal processing of sensory signals, with reduced inhibitory GABAergic signaling a likely key player. Our previous research demonstrated that spinal transplantation of GABAergic neural progenitor cells (NPCs) reduced neuropathic pain while intensive locomotor training (ILT) could reduce development of pain and partially reverse already established pain behaviors. Therefore, we evaluate the potential mutually beneficial anti-hypersensitivity effects of NPC transplants cells in combination with early or delayed ILT. NPC transplants were done at 4 weeks post-SCI. ILT, using a progressive ramping treadmill protocol, was initiated either 5 days post-SCI (early: pain prevention group) or at 5 weeks post-SCI (delayed: to reverse established pain) in male Sprague Dawley rats. Results showed that either ILT alone or NPCs alone could partially attenuate SCI neuropathic pain behaviors in both prevention and reversal paradigms. However, the combination of ILT with NPC transplants significantly enhanced neuropathic pain reduction on most of the outcome measures including tests for allodynia, hyperalgesia, and ongoing pain. Immunocytochemical and neurochemical analyses showed decreased pro-inflammatory markers and spinal pathology with individual treatments; these measures were further improved by the combination of either early or delayed ILT and GABAergic cellular transplantation. Lumbar dorsal horn GABAergic neuronal and process density were nearly restored to normal levels by the combination treatment. Together, these interventions may provide a less hostile and more supportive environment for promoting functional restoration in the spinal dorsal horn and attenuation of neuropathic pain following SCI. These findings suggest mutually beneficial effects of ILT and NPC transplants for reducing SCI neuropathic pain.


Assuntos
Neurônios GABAérgicos/transplante , Atividade Motora/fisiologia , Células-Tronco Neurais/transplante , Neuralgia/terapia , Condicionamento Físico Animal/fisiologia , Traumatismos da Medula Espinal/terapia , Medula Espinal/patologia , Animais , Transplante de Células , Modelos Animais de Doenças , Masculino , Neuralgia/etiologia , Neuralgia/patologia , Limiar da Dor/fisiologia , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/patologia , Resultado do Tratamento
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