RESUMO
Drug treatments for pain often do not outperform placebo, and a better understanding of placebo mechanisms is needed to improve treatment development and clinical practice. In a large-scale fMRI study (N = 392) with pre-registered analyses, we tested whether placebo analgesic treatment modulates nociceptive processes, and whether its effects generalize from conditioned to unconditioned pain modalities. Placebo treatment caused robust analgesia in conditioned thermal pain that generalized to unconditioned mechanical pain. However, placebo did not decrease pain-related fMRI activity in brain measures linked to nociceptive pain, including the Neurologic Pain Signature (NPS) and spinothalamic pathway regions, with strong support for null effects in Bayes Factor analyses. In addition, surprisingly, placebo increased activity in some spinothalamic regions for unconditioned mechanical pain. In contrast, placebo reduced activity in a neuromarker associated with higher-level contributions to pain, the Stimulus Intensity Independent Pain Signature (SIIPS), and affected activity in brain regions related to motivation and value, in both pain modalities. Individual differences in behavioral analgesia were correlated with neural changes in both modalities. Our results indicate that cognitive and affective processes primarily drive placebo analgesia, and show the potential of neuromarkers for separating treatment influences on nociception from influences on evaluative processes.
Assuntos
Encéfalo , Cognição , Imageamento por Ressonância Magnética , Dor Nociceptiva , Efeito Placebo , Humanos , Masculino , Feminino , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Dor Nociceptiva/fisiopatologia , Dor Nociceptiva/psicologia , Adulto Jovem , Nociceptividade/efeitos dos fármacos , Nociceptividade/fisiologia , Teorema de Bayes , Analgesia/métodos , Afeto/fisiologia , Afeto/efeitos dos fármacos , Analgésicos/uso terapêutico , Analgésicos/farmacologiaRESUMO
BACKGROUND: Pain is a common symptom in patients with advanced, metastatic, or terminal cancer. Neuropathic pain and psycho-emotional suffering are factors that increase the difficulty of pain management. Pain control in patients with cancer remains a challenge for medical professionals. STUDY QUESTION: What is the evolution of neuropathic/mixed pain compared with nociceptive pain under standardized treatment in patients with cancer? STUDY DESIGN: A prospective, longitudinal, open-label, nonrandomized study was conducted on patients with cancer pain. MEASURES AND OUTCOMES: Pain type was assessed at admission using the modified Brief Pain Inventory, and pain intensity was assessed daily using the Numerical Rating Scale for 14 days and on days 21 and 28. Screening of depression was performed on days 1, 7, 14, 21, and 28 using the Hamilton Depression Rating Scale. Patients with pain and depression received analgesics with antidepressants, while patients without depression received analgesics or analgesics with an anticonvulsant depending on the pain subtype. RESULTS: Of 72 patients, 23 had nociceptive pain and 49 had neuropathic/mixed pain. At admission, pain intensity was higher for patients with neuropathic/mixed pain compared with nociceptive pain (mean values: 7.06 vs. 5.82) with statistical significance ( P = 0.001) and remained as such at the end of this study (mean values: 3.77 vs. 2.73). A decrease in the mean pain intensity was observed in all types of pain, but without statistical significance regardless of pain type and treatment protocol used ( P = 0.77). If depression was present, antidepressants combined with analgesics decreased pain and depression scores significantly ( P = 0.001). CONCLUSIONS: Patients with neuropathic/mixed pain have higher levels of pain and lower response to treatment. Identifying psycho-emotional suffering can improve pain control by intervening in the physical and psycho-emotional components of pain.
Assuntos
Dor do Câncer , Neuralgia , Dor Nociceptiva , Cuidados Paliativos , Analgésicos/uso terapêutico , Dor do Câncer/tratamento farmacológico , Dor do Câncer/psicologia , Depressão/diagnóstico , Depressão/tratamento farmacológico , Humanos , Estudos Longitudinais , Neuralgia/tratamento farmacológico , Neuralgia/psicologia , Dor Nociceptiva/tratamento farmacológico , Dor Nociceptiva/psicologia , Cuidados Paliativos/métodos , Estudos ProspectivosRESUMO
Chronic neuropathic pain affects 7-10 % of the population and is often accompanied by comorbid emotional disorders, which greatly reduce the quality of life of the patients, impairing physical, cognitive, emotional, and social functioning. Despite the higher prevalence and severity of chronic pain in women, the number of publications using female animals remains scarce. While in the chronic constriction injury (CCI) model the development of mechanical/thermal hyperalgesia, allodynia and spontaneous pain has been shown in both sexes, little is known on CCI-induced emotional impairments and sciatic nerve histopathology in female rats, as well as on the contributions of ovarian hormones to peripheral nerve injury. In this work, young adult rats (Wistar Han) were assigned to one of five groups: gonadally intact females (SHAM/SHAM), ovariectomized females (SHAM/OVX), gonadally intact females with CCI (CCI/SHAM); ovariectomized females with CCI (CCI/OVX) and males with CCI (CCIM). In the postoperative period, CCI animals, both females and males, displayed visible gait abnormalities, limping and guarding the affected hind paw although locomotion was not affected. Neuropathic females developed sustained mechanical allodynia, with CCI/OVX animals displaying symptoms two weeks before CCI/SHAM females. Interestingly, regarding mechanical and cold allodynia, CCI males slowly recovered from week 3 onwards. While CCI induced neither anxiety- nor depressive-like behaviour in females, ovariectomy per se induced anhedonic-like behaviour, regardless of CCI surgery. Histopathological analysis of the sciatic nerve showed CCI induced nerve damage, fibrosis, myelin sheath degradation and inflammation. Single-cell electrophysiological data from the rostral ventromedial medulla (RVM) suggests this area is partly involved in descending facilitation associated with experimental neuropathic pain. Altogether, our findings demonstrate CCI females display distinct sensory, emotional, electrophysiological, and histopathological impairments from males, and that ovariectomy aggravates females' responses to peripheral nerve injury.
Assuntos
Neuralgia/fisiopatologia , Dor Nociceptiva/fisiopatologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Caracteres Sexuais , Animais , Ansiedade/etiologia , Depressão/etiologia , Modelos Animais de Doenças , Feminino , Masculino , Neuralgia/psicologia , Dor Nociceptiva/psicologia , Traumatismos dos Nervos Periféricos/psicologia , Ratos , Ratos Wistar , Nervo Isquiático/lesõesRESUMO
Recent studies have shown that the endogenous opioid system is considerably affected by early life stress such as child abuse. Here, we investigated whether early life stress changes the endogenous opioid receptors and their peptides, and if such stress impacts morphine antinociception. We used mice affected by maternal separation and social isolation (MSSI) as an early life stress model. In the tail-flick test, 10-week-old MSSI mice showed a significant decrease in morphine antinociception compared to age-matched control mice. The number of c-Fos-positive cells increased in the periaqueductal gray (PAG), nucleus accumbens, and thalamus of control mice after the morphine injections, whereas hardly any positive cells were detected in the same areas of MSSI mice. The expression of µ- and κ-opioid receptor (MOR and KOR, respectively) messenger RNA (mRNA) was significantly decreased in the PAG of MSSI mice, whereas KOR expression was significantly increased in the amygdala of MSSI mice. The expression of δ-opioid receptor (DOR) mRNA was significantly reduced in the PAG and rostral ventromedial medulla of MSSI mice compared to control mice. Moreover, the lack of morphine antinociception was observed in 18-week-old MSSI mice. Our findings suggest that the supraspinal opioid system may be affected by early life stress exposure, and that this exposure may impact morphine antinociception.
Assuntos
Analgésicos Opioides/farmacologia , Encéfalo/efeitos dos fármacos , Morfina/farmacologia , Nociceptividade/efeitos dos fármacos , Dor Nociceptiva/prevenção & controle , Receptores Opioides delta/agonistas , Receptores Opioides mu/agonistas , Estresse Psicológico/metabolismo , Fatores Etários , Animais , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Masculino , Privação Materna , Camundongos , Dor Nociceptiva/metabolismo , Dor Nociceptiva/fisiopatologia , Dor Nociceptiva/psicologia , Gravidez , Proteínas Proto-Oncogênicas c-fos/metabolismo , Receptores Opioides delta/genética , Receptores Opioides delta/metabolismo , Receptores Opioides mu/genética , Receptores Opioides mu/metabolismo , Transdução de Sinais , Isolamento Social , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologiaRESUMO
OBJECTIVES: Peripherally directed treatments (targeted exercise, surgery) can reduce, but not fully eliminate, pain for up to 40% of patients with Achilles tendinopathy. The objectives of the present study were (1) to identify indicators of altered central processing in participants with Achilles tendinopathy compared to controls, and (2) to determine which indicators of altered central processing would persist after a local anesthetic injection in patients with Achilles tendinopathy. DESIGN: Mechanistic clinical trial. METHODS: Forty-six adults (23 with chronic Achilles tendinopathy, 23 matched controls) repeated (1) a movement-evoked pain rating, (2) motor performance assessment, (3) pain psychology questionnaires, and (4) quantitative sensory testing. Participants with Achilles tendinopathy received a local anesthetic injection before repeat testing and controls did not. Mixed-effects analyses of variance examined the effects of group, time, and group by time. RESULTS: The Achilles tendinopathy group had movement-evoked pain, motor dysfunction, and higher pain psychological factors (pain catastrophizing, kinesiophobia) compared to controls (P<.05). The Achilles tendinopathy group did not have indicators of nociplastic pain with quantitative sensory testing (P>.05). In those with Achilles tendinopathy, local anesthetic injection eliminated pain and normalized the observed deficits in heel-raise performance and pain catastrophizing (group-by-time effect, P<.01), but not in kinesiophobia (P = .45). Injection did not affect measures of nociplastic pain (P>.05). CONCLUSION: People with Achilles tendinopathy had elevated pain psychological factors and motor dysfunction but no signs of nociplastic pain with quantitative sensory testing. Removal of nociceptive input normalized movement-evoked pain and some indicators of altered central processing (motor dysfunction, pain catastrophizing), but not kinesiophobia. J Orthop Sports Phys Ther 2020;50(6):334-343. Epub 29 Apr 2020. doi:10.2519/jospt.2020.9242.
Assuntos
Tendão do Calcâneo , Anestésicos Locais/administração & dosagem , Catastrofização , Dor Nociceptiva/prevenção & controle , Dor Nociceptiva/psicologia , Tendinopatia/fisiopatologia , Tendão do Calcâneo/diagnóstico por imagem , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Ropivacaina/administração & dosagem , Tendinopatia/diagnóstico por imagem , UltrassonografiaRESUMO
Neuropathic pain is a complex disorder associated with emotional and cognitive deficits that may impair nociceptive manifestations. There is high inter-individual variability in the manifestations of human neuropathic pain, which largely depends on personality traits. We aim to identify the influence of different behavioral traits in the inter-individual vulnerability to neuropathic pain manifestations using behavioral, electrophysiological and genetic approaches. We first selected mice with extreme social and emotional traits and look for correlation with the spontaneous neuronal activity in the central amygdala. Neuropathic pain was induced to these mice to evaluate the influence of behavioral traits on nociceptive manifestations and gene expression profiles in the amygdala. Our results show an association of the spontaneous central amygdala neuronal activity with the sociability behavior. We demonstrate that low sociable, high anxious and low depressive phenotypes develop enhanced nociceptive hypersensitivity after nerve injury. However, greater emotional alterations and cognitive impairment are observed in high sociable, anxious-like and depressive-like mice, indicating that nociceptive, emotional and cognitive manifestations of neuropathic pain do not correlate with each other. Gene analyses identify high Pdyn and Il6 levels in the amygdala as indicative of enhanced nociceptive hypersensitivity and reveal an association between high Gadd45 expression and attenuated emotional and cognitive manifestations of neuropathic pain.
Assuntos
Cognição/fisiologia , Emoções/fisiologia , Individualidade , Neuralgia/fisiopatologia , Neuralgia/psicologia , Dor Nociceptiva/psicologia , Animais , Comportamento Animal , Proteínas de Ciclo Celular/biossíntese , Núcleo Central da Amígdala/metabolismo , Núcleo Central da Amígdala/fisiologia , Encefalinas/metabolismo , Expressão Gênica , Interleucina-6/metabolismo , Masculino , Camundongos , Neuralgia/complicações , Dor Nociceptiva/complicações , Precursores de Proteínas/metabolismo , Comportamento SocialRESUMO
INTRODUCTION: The differentiation between acute and chronic pain can be insufficient for appropriate pain management. The aim of this study was to evaluate the prevalence of the predominant pain type (nociceptive, neuropathic, or central sensitization [CS] pain) in breast cancer survivors (BCS) with chronic pain. The secondary aims were to examine (1) differences in health-related quality of life (HRQoL) between the different pain groups; and (2) the associations between patient-, disease-, and treatment-related factors and the different pain types. METHODS: To determine the prevalence of the predominant type of pain, a recently proposed classification system was used. BCS were asked to complete the VAS for pain, Douleur Neuropathique 4 Questionnaire, Margolis Pain Diagram, Central Sensitization Inventory, and Short Form 36 (SF-36). RESULTS: Ninety-one BCS participated, among whom 25.3% presented neuropathic pain, 18.7% nociceptive pain, and 15.4% CS pain. Mixed pain was found in 40.6%. A significant intergroup difference in HRQoL was found for SF-36 "general health" (P = 0.04). The odds for the presence of CS rather than nociceptive pain are 26 times higher in patients exposed to hormone therapy in comparison to the nonexposed (odds ratio 25.95, 95% confidence interval 1.33 to 504.37, P = 0.03). CONCLUSION: Neuropathic pain is most frequent in BCS. Strong associations were found between CS pain and hormone therapy.
Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Sensibilização do Sistema Nervoso Central , Dor Crônica/epidemiologia , Neuralgia/epidemiologia , Dor Nociceptiva/epidemiologia , Adulto , Idoso , Dor Crônica/etiologia , Dor Crônica/psicologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Neuralgia/etiologia , Neuralgia/psicologia , Dor Nociceptiva/etiologia , Dor Nociceptiva/psicologia , Prevalência , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
The persistent activation of N-methyl-d-aspartate acid receptors (NMDARs) seems to be responsible for a series of changes in neurons associated with neuropathic pain, including the failure of opioids that act through mu-opioid receptors (MORs) to provide efficacious pain relief. As the noradrenergic locus coeruleus (LC) forms part of the endogenous analgesic system, we explored how intra-LC administration of morphine, a MORs agonist, alone or in combination with MK-801, a NMDARs antagonist, affects the sensorial and affective dimension of pain in a rat model of neuropathic pain; chronic constriction injury (CCI). Intra-LC microinjection of morphine induced analgesia in CCI rats, as evident in the von Frey and cold plate test 7 and 30â¯days after surgery, although it was not able to reverse pain-related aversion when evaluated using the place escape/avoidance test. However, the thermal anti-nociception produced by morphine was enhanced when it was administered to the LC of CCI animals in combination with MK-801, without altering its effects on the mechanical thresholds. Furthermore, pain-related aversion was reduced by co-administration of these agents, yet only in the short-term CCI (7â¯day) rats. Overall the data indicate that administration of morphine to the LC produces analgesia in nerve injured animals and that this effect is potentiated in specific pain modalities by the co-administration of MK-801. While a combination of morphine and MK-801 could reduce pain-related aversion in short-term neuropathic animals, it was ineffective in the long-term, suggesting that its sensorial effects and its influence on the affective component of pain are regulated by different mechanisms.
Assuntos
Analgésicos Opioides/farmacologia , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Locus Cerúleo/efeitos dos fármacos , Morfina/farmacologia , Neuralgia/tratamento farmacológico , Animais , Ansiedade/tratamento farmacológico , Ansiedade/fisiopatologia , Constrição Patológica , Modelos Animais de Doenças , Quimioterapia Combinada , Locus Cerúleo/fisiopatologia , Masculino , Neuralgia/fisiopatologia , Neuralgia/psicologia , Dor Nociceptiva/tratamento farmacológico , Dor Nociceptiva/fisiopatologia , Dor Nociceptiva/psicologia , Ratos Sprague-Dawley , Neuropatia Ciática/tratamento farmacológico , Neuropatia Ciática/fisiopatologia , Neuropatia Ciática/psicologiaRESUMO
OBJECTIVE: Sensory disturbances are common in chronic pain patients. Hyperacusis can be an especially debilitating experience. Here, we review published work on how the auditory and nociceptive systems might interact in chronic pain syndromes to produce pain-hyperacusis. DESIGN: Literature review. STUDY SAMPLE: The PubMed and Scopus databases were searched for relevant articles published between 2000 and 2017 using the primary search terms "hyperacusis"/"hyperacousis" and "pain". Ten papers were found using this strategy. Supplementary sources were identified by browsing textbooks and the reference lists of identified articles. RESULTS: The importance of central mechanisms in pain-hyperacusis was highlighted in the 10 selected papers. Hyperacusis is a significant but under-recognised symptom in conditions such as complex regional pain syndrome and fibromyalgia, and an integral feature of migraine. CONCLUSIONS: Nociceptive circuits become hypersensitive in acute and chronic pain; this sensitivity spreads from the periphery to spinal neurons and higher centres in the brain, leading to hyperalgesia or spontaneous pain even in the absence of peripheral nociceptive input. This "central sensitisation" may alter activity at sensory convergence points in the thalamus and brainstem centres such as the locus coeruleus, and give rise to hyperacusis in certain pain syndromes.
Assuntos
Vias Auditivas/fisiopatologia , Encéfalo/fisiopatologia , Dor Crônica/fisiopatologia , Audição , Hiperacusia/fisiopatologia , Dor Nociceptiva/fisiopatologia , Nociceptores , Limiar da Dor , Adaptação Fisiológica , Limiar Auditivo , Dor Crônica/diagnóstico , Dor Crônica/epidemiologia , Dor Crônica/psicologia , Humanos , Hiperacusia/diagnóstico , Hiperacusia/epidemiologia , Hiperacusia/psicologia , Dor Nociceptiva/diagnóstico , Dor Nociceptiva/epidemiologia , Dor Nociceptiva/psicologia , Medição da Dor , Percepção da DorRESUMO
BACKGROUND: Clinical studies demonstrated peripheral nociceptor deficit in stress-related chronic pain states, such as fibromyalgia. The interactions of stress and nociceptive systems have special relevance in chronic pain, but the underlying mechanisms including the role of specific nociceptor populations remain unknown. We investigated the role of capsaicin-sensitive neurones in chronic stress-related nociceptive changes. METHOD: Capsaicin-sensitive neurones were desensitized by the capsaicin analogue resiniferatoxin (RTX) in CD1 mice. The effects of desensitization on chronic restraint stress (CRS)-induced responses were analysed using behavioural tests, chronic neuronal activity assessment in the central nervous system with FosB immunohistochemistry and peripheral cytokine concentration measurements. RESULTS: Chronic restraint stress induced mechanical and cold hypersensitivity and increased light preference in the light-dark box test. Open-field and tail suspension test activities were not altered. Adrenal weight increased, whereas thymus and body weights decreased in response to CRS. FosB immunopositivity increased in the insular cortex, dorsomedial hypothalamic and dorsal raphe nuclei, but not in the spinal cord dorsal horn after the CRS. CRS did not affect the cytokine concentrations of hindpaw tissues. Surprisingly, RTX pretreatment augmented stress-induced mechanical hyperalgesia, abolished light preference and selectively decreased the CRS-induced neuronal activation in the insular cortex. RTX pretreatment alone increased the basal noxious heat threshold without influencing the CRS-evoked cold hyperalgesia and augmented neuronal activation in the somatosensory cortex and interleukin-1α and RANTES production. CONCLUSIONS: Chronic restraint stress induces hyperalgesia without major anxiety, depression-like behaviour or peripheral inflammatory changes. Increased stress-induced mechanical hypersensitivity in RTX-pretreated mice is presumably mediated by central mechanisms including cortical plastic changes. SIGNIFICANCE: These are the first data demonstrating the complex interactions between capsaicin-sensitive neurones and chronic stress and their impact on nociception. Capsaicin-sensitive neurones are protective against stress-induced mechanical hyperalgesia by influencing neuronal plasticity in the brain.
Assuntos
Capsaicina/farmacologia , Diterpenos/farmacologia , Hiperalgesia/etiologia , Nociceptividade/efeitos dos fármacos , Dor Nociceptiva/etiologia , Estresse Psicológico/complicações , Animais , Capsaicina/análogos & derivados , Temperatura Baixa , Modelos Animais de Doenças , Temperatura Alta , Hiperalgesia/psicologia , Masculino , Camundongos , Dor Nociceptiva/prevenção & controle , Dor Nociceptiva/psicologia , Nociceptores/efeitos dos fármacos , Nociceptores/fisiologia , Restrição FísicaRESUMO
A new operant test for preclinical pain research, termed the Mechanical Conflict System (MCS), is presented. Rats were given a choice either to remain in a brightly lit compartment or to escape to a dark compartment by crossing an array of height-adjustable nociceptive probes. Latency to escape the light compartment was evaluated with varying probe heights (0, .5, 1, 2, 3, and 4 mm above compartment floor) in rats with neuropathic pain induced by constriction nerve injury (CCI) and in naive control rats. Escape responses in CCI rats were assessed following intraperitoneal administration of pregabalin (10 and 30 mg/kg), morphine (2.5 and 5 mg/kg), and the tachykinin NK1 receptor antagonist, RP 67580 (1 and 10 mg/kg). Results indicate that escape latency increased as a function of probe height in both naive and CCI rats. Pregabalin (10 and 30 mg/kg) and morphine (5 mg/kg), but not RP 67580, decreased latency to escape in CCI rats suggesting an antinociceptive effect. In contrast, morphine (10 mg/kg) but not pregabalin (30 mg/kg) increased escape latency in naive rats suggesting a possible anxiolytic action of morphine in response to light-induced fear. No order effects following multiple test sessions were observed. We conclude that the MCS is a valid method to assess behavioral signs of affective pain in rodents.
Assuntos
Aprendizagem da Esquiva/fisiologia , Condicionamento Operante , Conflito Psicológico , Reação de Fuga/fisiologia , Etologia/instrumentação , Traumatismos do Pé/fisiopatologia , Hiperalgesia/fisiopatologia , Dor Nociceptiva/fisiopatologia , Analgésicos/administração & dosagem , Analgésicos/uso terapêutico , Animais , Ansiolíticos/administração & dosagem , Ansiolíticos/uso terapêutico , Comportamento de Escolha , Condicionamento Operante/fisiologia , Escuridão , Relação Dose-Resposta a Droga , Medo , Traumatismos do Pé/psicologia , Hiperalgesia/etiologia , Hiperalgesia/psicologia , Injeções Intraperitoneais , Isoindóis/administração & dosagem , Isoindóis/uso terapêutico , Ligadura , Luz/efeitos adversos , Masculino , Morfina/administração & dosagem , Morfina/uso terapêutico , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Neuralgia/fisiopatologia , Antagonistas dos Receptores de Neurocinina-1/administração & dosagem , Antagonistas dos Receptores de Neurocinina-1/uso terapêutico , Dor Nociceptiva/tratamento farmacológico , Dor Nociceptiva/psicologia , Pregabalina/administração & dosagem , Pregabalina/uso terapêutico , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Nervo Isquiático/lesões , Nervo Isquiático/fisiopatologiaRESUMO
CONTEXT: Cajanus cajan L. (Fabaceae), a food crop, is widely used in traditional medicine. OBJECTIVES: The phytochemical composition of C. cajan seeds and evaluation of the anti-inflammatory, immunomodulatory, antinociceptive, and antioxidant activities were studied. MATERIALS AND METHODS: Unsaponifiable matter and fatty acids were analyzed by GC and GC/MS. The n-butanol fraction was chromatographed on polyamide column. The anti-inflammatory activity of hexane extract (200 and 400 mg/kg, p.o.) was evaluated using the carrageenan-induced rat paw edema at 1, 2, and 3 h. The serum tumor necrosis factor-α, interleukin-6, and immunoglobulin G levels were detected by ELISA. The hexane extract antinociceptive activity was determined by adopting the writhing test in mice. DPPH radical scavenging, total reduction capability, and inhibition of lipid peroxidation of butanol fraction were evaluated. RESULTS AND CONCLUSION: Twenty-one unsaponifiable compounds (mainly phytol, 2,6-di-(t-butyl)-4-hydroxy-4-methyl-2,5-cyclohexadiene-1-one, ß-sitosterol, stigmasterol, and campesterol), as well as 12 fatty acids (primarily 9,12-octadecadienoic and palmitic acids) were identified in hexane extract of C. cajan seeds. n-BuOH fraction contains quercetin-3-O-ß-d-glucopyranoside, orientin, vitexin, quercetin, luteolin, apigenin, and isorhamnetin. For the first time, quercetin-3-O-ß-d-glucopyranoside is isolated from C. cajan plant. The hexane extract (200 and 400 mg/kg) inhibited carrageenan-induced inflammation by 85 and 95%, respectively, 3 h post-carrageenan challenge. This was accompanied by an 11 and 20%, 8 and 13%, respectively, decrease of TNF-α and IL-6, as well as significant decrease in IgG serum levels. Moreover, hexane extract (200 and 400 mg/kg) decreased the number of writhings by 61 and 83%, respectively. The butanol fraction showed DPPH radical scavenging (inhibitory concentration (IC50) value: 9.07 µg/ml).
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Fatores Imunológicos/farmacologia , Inflamação/prevenção & controle , Dor Nociceptiva/prevenção & controle , Extratos Vegetais/farmacologia , Analgésicos/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Comportamento Animal/efeitos dos fármacos , Compostos de Bifenilo/química , Butanóis/química , Cajanus/química , Carragenina , Citocinas/sangue , Modelos Animais de Doenças , Egito , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Hexanos/química , Fatores Imunológicos/isolamento & purificação , Inflamação/sangue , Inflamação/induzido quimicamente , Mediadores da Inflamação/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Dor Nociceptiva/etiologia , Dor Nociceptiva/psicologia , Fitoterapia , Picratos/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Ratos , Sementes , Solventes/química , Fatores de TempoRESUMO
Osteoid osteoma is a benign bone tumour usually found in the lower extremities of children and young adults. This tiny bone tumour causes pain out of all proportion to its size and hinders the daily activities. This Quasi-experimental study conducted in the department of Orthopaedic surgery of BSMMU from January 2008 to December 2009. Twenty one patients were included in the study where purposive sampling technique was used on the basis of inclusion and exclusion criteria and all the ethical conditions were fulfilled. Diagnosis was almost obtained by taking history, clinical examination, and relevant investigations. Clinical variables were age, sex, site, pain, swelling, deformity and outcome variables were painless active life, removal of swelling, prevention of deformity, rate of recurrence. After localization of the tumour with the help of C arm, the nidus was excised in a small block of bone. The outcome is categorized by consensus, as clinically successful, only if the patient was free of pain and was taking no medication. The treatment was considered to have failed if a subsequent procedure had been performed to remove tumour. Among 21 cases, 14(66.7%) were male and 7(33.7%) were female. Maximum number of patients 15(71.4%) was between 10 years to 20 years. Most of the patients (76.2%) affected by osteoid osteoma were young students and most of the patients (95.2%) experienced moderate aching pain, usually aggravating at night which was typically relieved by aspirin or other NSAIDs (71.4%). Lower limbs (76.2%) particularly femur and tibia were commonly affected. Out of 21 patients, 19(90.5%) patients have got immediate pain relief or required no medication. In only 2 patients (9.5%), subsequent procedure has been performed to relief pain. So, successful outcome (in 19 out of 21) was significantly (p<0.001) higher in comparison to failed. Surgical excision of the nidus is a simple and easy procedure and does not require extensive resection of bone. If localization is done properly success rate is high and patients can return to normal daily activities.
Assuntos
Neoplasias Ósseas , Dissecação , Dor Nociceptiva , Osteoma Osteoide , Dor Pós-Operatória , Adolescente , Neoplasias Ósseas/complicações , Neoplasias Ósseas/patologia , Neoplasias Ósseas/fisiopatologia , Neoplasias Ósseas/cirurgia , Dissecação/efeitos adversos , Dissecação/métodos , Feminino , Deformidades Adquiridas do Pé/etiologia , Deformidades Adquiridas do Pé/prevenção & controle , Humanos , Ossos da Perna/patologia , Ossos da Perna/cirurgia , Masculino , Dor Nociceptiva/diagnóstico , Dor Nociceptiva/psicologia , Osteoma Osteoide/complicações , Osteoma Osteoide/patologia , Osteoma Osteoide/fisiopatologia , Osteoma Osteoide/cirurgia , Medição da Dor/métodos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/fisiopatologia , Qualidade de Vida , Recuperação de Função Fisiológica , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: To investigate the role of the synthetic steroid tibolone in the progression of osteoarthritis (OA) and in nociceptive behaviour in an experimental rat model of OA and ovariectomy (OVX)-induced osteoporosis. METHODS: OA was induced in Wistar rats by anterior cruciate ligament transection (ACLT) of the right knee. Osteoporosis was induced by bilateral OVX. Groups of animals were subjected to ACLT, OVX, sham or OVX + ACLT. In addition, two groups were subjected to OVX + ACLT surgeries and were orally administered 0.1 or 0.5 mg tibolone every other day for 14 consecutive weeks, starting 6 weeks after surgery. Nociceptive behaviours (secondary mechanical allodynia and weight-bearing distribution of the hind paws) were analysed prior to and every 3 weeks after surgery up to 24 weeks. At 24 weeks, histopathological studies were performed on the cartilage and synovial membranes of the knee joints, and bone metabolism was assessed by measuring serum concentrations of calcium, phosphorus and alkaline phosphatase. RESULTS: Rats undergoing ACLT or OVX + ACLT surgeries showed obvious OA changes in the joints. Animals subjected to ACLT + OVX and treated with tibolone had significantly less cartilage degeneration and synovitis and showed improved nociceptive tests compared with animals undergoing ACLT + OVX surgeries alone. OVX increased the severity of the ACLT-induced OA changes. There was a significant increase in serum alkaline phosphatase in the tibolone-treated ACLT + OVX groups. CONCLUSIONS: Treatment with tibolone attenuated the development of OA, concomitantly reduced nociception and increased serum alkaline phosphatase in ACLT + OVX rats.
Assuntos
Analgésicos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Dor Nociceptiva/tratamento farmacológico , Dor Nociceptiva/psicologia , Norpregnenos/uso terapêutico , Osteoartrite/tratamento farmacológico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Animais , Lesões do Ligamento Cruzado Anterior , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Feminino , Articulações/patologia , Osteoartrite/patologia , Ovariectomia , Ratos , Ratos Wistar , Suporte de CargaRESUMO
UNLABELLED: Early-life stress is associated with an increased risk of developing affective disorders and chronic pain conditions. This study examined the effect of maternal deprivation (MD) on nociceptive responding prior to and following peripheral nerve injury (L5-L6 spinal nerve ligation [SNL]). Because neuroimmune signaling plays an important role in pain and affective disorders, associated alterations in glial and cytokine expression were assessed in key brain regions associated with emotional and nociceptive responding, the hippocampus and prefrontal cortex. MD female, but not male, rats exhibited thermal hypoalgesia and mechanical allodynia compared with control (non-MD) counterparts. SNL resulted in mechanical and cold allodynia in MD and control rats of both sexes. However, MD females exhibited enhanced SNL-induced allodynic responding compared with non-MD counterparts. Interleukin 6 (IL-6) expression was reduced in the prefrontal cortex of MD-SNL males when compared with non-SNL counterparts. Glial fibrillary acidic protein and IL-1ß expression in the hippocampus of MD-SNL males was increased compared with non-MD controls. MD-SNL females exhibited reduced tumor necrosis factor alpha in the prefrontal cortex with a concomitant increase in IL-6 and tumor necrosis factor alpha expression in the hippocampus, compared with either MD or SNL alone. In conclusion, MD female, but not male, rats exhibit enhanced nociceptive responding following peripheral nerve injury, effects that may relate to the distinct neuroinflammatory profile observed in female versus male rats. PERSPECTIVE: This study demonstrates that females rats exposed to early-life stress exhibit enhanced neuropathic pain responding, effects that are associated with alterations in neuroinflammatory mediators. Increased understanding of the interactions among early-life stress, gender, and pain may lead to the identification of novel therapeutic targets for the treatment of chronic pain disorders.
Assuntos
Mediadores da Inflamação/metabolismo , Privação Materna , Dor/psicologia , Traumatismos dos Nervos Periféricos/metabolismo , Traumatismos dos Nervos Periféricos/psicologia , Animais , Ansiedade/psicologia , Comportamento Animal , Citocinas/biossíntese , Comportamento Exploratório , Feminino , Hipocampo/metabolismo , Ligadura , Ativação de Macrófagos , Masculino , Atividade Motora , Neuralgia/metabolismo , Neuralgia/psicologia , Neuroglia/fisiologia , Sistemas Neurossecretores/fisiopatologia , Dor Nociceptiva/metabolismo , Dor Nociceptiva/psicologia , Medição da Dor , Córtex Pré-Frontal/metabolismo , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Caracteres Sexuais , Nervos Espinhais/patologiaRESUMO
OBJECTIVE: To identify and compare perceptions of pain and how it is faced between men and women with central post-stroke pain. METHODS: The participants were 25 men and 25 women of minimum age 30 years-old and minimum schooling level of four years, presenting central post-stroke pain for at least three months. The instruments used were: Mini-Mental State Examination; structured interview for the Brief Psychiatric Scale; Survey of Sociodemographic and Clinical Data; Visual Analogue Scale (VAS); Ways of Coping with Problems Scale (WCPS) in Scale; Revised Illness Perception Questionnaire (IPQ-R); and Beck Depression Inventory (BDI). RESULTS: A significantly greater number of women used the coping strategy "Turn to spiritual and religious activities" in WCPS. They associated their emotional state with the cause of pain in IPQ-R. "Distraction of attention" was the strategy most used by the subjects. CONCLUSION: Women used spiritual and religious activities more as a coping strategy and perceived their emotional state as the cause of pain.
OBJETIVO: Identificar e comparar a percepção e o enfrentamento da dor entre homens e mulheres com dor central por acidente vascular cerebral (AVC). MÉTODOS: Participaram do estudo 25 homens e 25 mulheres com dor central por AVC há pelo menos três meses, maiores de 30 anos, escolaridade mínima de 4ª série. Os instrumentos utilizados foram: Mini-exame do Estado Mental; Entrevista Estruturada para Escala Psiquiátrica Breve; Inquérito de Dados Sociodemográficos e Clínicos; Escala Visual Analógica (EVA); Escala dos Modos de Enfrentamento de Problemas (EMEP); Questionário de Percepção da Doença Revisado (QPD-R) e Inventário de Depressão de Beck (IDB). RESULTADOS: Um número significativamente maior de mulheres revelou usar a estratégia de enfrentamento "Realizar atividades espirituais e religiosas" na EMEP e associou o estado emocional à causa de suas dores no QPD-R. "Distração da atenção" foi a estratégia mais utilizada pelos sujeitos. CONCLUSÃO: As mulheres utilizaram mais atividades espirituais e religiosas como estratégia de enfrentamento e perceberam mais o estado emocional como causa da dor.
Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adaptação Psicológica/fisiologia , Cognição/fisiologia , Dor Nociceptiva/etiologia , Acidente Vascular Cerebral/complicações , Dor Nociceptiva/psicologia , Medição da Dor , Religião e Psicologia , Fatores Sexuais , Fatores Socioeconômicos , Inquéritos e Questionários , Acidente Vascular Cerebral/fisiopatologia , Fatores de TempoRESUMO
Endokinins designated from the human TAC4 gene consist of endokinin A, endokinin B, endokinin C (EKC) and endokinin D (EKD). EKC/D is a peptide using the common carboxyl-terminal in EKC and EKD and consists of 12 amino acids, and exerts antagonistic effects on the induction of scratching behavior by substance P (SP). Some of SP-preferring receptor antagonists have several d-tryptophan (d-Trp); however, the pharmacological effect of EKC/D-derived peptides with d-Trp remains to be solved. Therefore, to clarify the pharmacological characteristics of EKC/D-derived peptides, effects of pretreatment with these peptides on SP-induced scratching and thermal hyperalgesia, formalin-induced flinching and carrageenan-induced inflammation were evaluated. Intrathecal administration of [d-Trp(8)]-EKC/D and [d-Trp(10)]-EKC/D showed a markedly long inhibitory effect, at least 14 h, whereas the antagonistic effects of [d-Trp(8,10)]-EKC/D and EKC/D without d-Trp disappeared after 1h. Furthermore, the inhibitory effect of [d-Trp(10)]-EKC/D-derived peptides was dependent on the number of amino acids from the amino-terminus, and the more numerous the amino acids, the more marked the antagonistic effect. Thus, these results indicate that the effective duration of EKC/D-derived peptides is dependent on the number of d-Trp in the carboxyl-terminal region and the amino-terminal region regulates the antagonistic effect of EKC/D.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Dor Nociceptiva/tratamento farmacológico , Fragmentos de Peptídeos/farmacologia , Células do Corno Posterior/efeitos dos fármacos , Taquicininas/farmacologia , Sequência de Aminoácidos , Aminoácidos/química , Analgésicos/administração & dosagem , Animais , Anti-Inflamatórios/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Carragenina/efeitos adversos , Formaldeído/efeitos adversos , Humanos , Hiperalgesia/induzido quimicamente , Imuno-Histoquímica , Inflamação/induzido quimicamente , Inflamação/terapia , Injeções Subcutâneas , Masculino , Dor Nociceptiva/psicologia , Medição da Dor/métodos , Fragmentos de Peptídeos/administração & dosagem , Células do Corno Posterior/química , Proteínas Proto-Oncogênicas c-fos/química , Ratos , Ratos Sprague-Dawley , Substância P/efeitos adversos , Substância P/antagonistas & inibidores , Taquicininas/administração & dosagem , Fatores de Tempo , Triptofano/farmacologiaRESUMO
Regional (e.g., low back) and widespread chronic pain disorders are common in the general population and are known to be heritable. Recent research suggests that genetic factors increase the risk of developing chronic pain independent of the site of pain. Candidate gene studies have been conducted on key pathways to elucidate susceptibility genes that are likely to be involved in both the sensory and affective components of pain. Findings have been largely equivocal, predominantly due to small sample size, but larger studies of pain in general population samples are being conducted. Interesting candidate genes from animal models and monogenic pain disorders are beginning to emerge. Recent advances in genetics research have yet to make an impact in the pain field but provide considerable scope for future research efforts.
Assuntos
Dor Crônica/genética , Predisposição Genética para Doença , Dor Nociceptiva/genética , Transtornos Somatoformes/genética , Dor Crônica/fisiopatologia , Dor Crônica/psicologia , Fibromialgia/genética , Fibromialgia/fisiopatologia , Fibromialgia/psicologia , Estudo de Associação Genômica Ampla , Humanos , Dor Nociceptiva/fisiopatologia , Dor Nociceptiva/psicologia , Transtornos Somatoformes/fisiopatologia , Transtornos Somatoformes/psicologiaRESUMO
BACKGROUND: Tramadol and dihydrocodeine (DHC) are analgesics of step 2 WHO analgesic ladder (opioids for mild to moderate pain, weak opioids) frequently used in the treatment of cancer pain of moderate intensity. The aim of the study was to assess the impact of tramadol and DHC treatment on quality of life (QL) and performance status (PS) of patients with cancer pain. PATIENTS AND METHODS: Randomised, cross-over, clinical study of 40 opioid-naive patients with nociceptive cancer pain who received tramadol or DHC controlled release tablets for 7 days, and then drugs were switched and administered for another 7 days. Pain was assessed by visual analogue scale (VAS), QL by EORTC QLQ C 30, and PS by Eastern Cooperative Oncology Group (ECOG) and Karnofsky. RESULTS: From 40 patients recruited, 30 completed the study. DHC treatment provided better analgesia (VAS). In QL functional scales, better emotional functioning in tramadol group and better global QL and cognitive functioning in DHC group were observed. In symptom scales, less fatigue, pain and sleep disturbances, less nausea and vomiting and better appetite in DHC group were noted. In tramadol group, less constipation and less financial problems were observed. No differences in dyspnoea and diarrhoea were noted. ECOG and Karnofsky PS were low and did not differ between tramadol and DHC groups. CONCLUSIONS: Dihydrocodeine treatment was associated with better global QL, cognitive functioning, analgesia and appetite, less fatigue, sleep disturbances, nausea and vomiting. Tramadol therapy was connected with better emotional functioning, less constipation and financial problems. PS deteriorated in both tramadol and DHC groups.