The effect of somatic pain and comorbid mental distress on oral health-related quality of life in orthodontic patients.

OBJECTIVES: The purpose of the present study was to evaluate the prevalence of somatic pain in orthodontic patients and determine whether somatic pain contributes to worsening oral health-related quality of life (OHRQoL) through the mediating effect of psychological discomfort. MATERIALS AND METHODS: Scale measurements and analyses were conducted on a cohort of 769 orthodontic outpatients, encompassing Patient Health Questionnaire-15-pain (PHQ-15-P), Hua-Xi Emotional-Distress Index (HEI), Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ), and Oral Health Impact Profile-14 (OHIP-14). RESULTS: Among the respondents, 56.3% (N = 433) reported somatic pain and 20.0% (N = 154) had mental discomfort based on PHQ-15-P and HEI scores. Patients with somatic pain symptoms had significantly higher scores of HEI and OHIP-14 (P < 0.001), and higher PHQ-15-P and HEI scores emerged as statistically significant predictors of lower OHIP-14 scores (P < 0.001). HEI scores which assessed anxiety and depression partially mediated the correlation between PHQ-15-P and OHIP-14 scores, of which anxiety accounted for 52.9% of the overall mediation effect, dominating the indirect effect. CONCLUSION: Orthodontic patients reporting somatic pains were at a significantly higher risk of worsening OHRQoL during treatment, and this adverse effect is partially mediated by anxiety and depression. CLINICAL RELEVANCE: Our findings highlight the necessity for the assessment of general health and mental well-being during orthodontic interventions. To prevent delays in treating general disorders and the potential failure of orthodontic treatments, we encourage increased attentiveness towards patients with somatic symptoms and consideration of the adverse effects of comorbid mental distress.

Neuropathic and Nociplastic Pain Profiles are Common in Adult Chronic Nonbacterial Osteitis (CNO).

Chronic nonbacterial osteitis (CNO) is a rare musculoskeletal disease causing chronic bone pain. It is known that chronic musculoskeletal pain may involve other mechanisms than nociceptive pain only. We investigate the prevalence of neuropathic and nociplastic pain in adult CNO and their association with clinical characteristics and treatment outcomes. Survey study among the Dutch adult CNO cohort (n = 84/195 participated), including PAIN-detect for neuropathic pain, and the Central Sensitization Inventory (CSI), Fibromyalgia Rapid Screening Tool (FiRST), and ACTTION-APS Pain Taxonomy (AAPT) for nociplastic pain. Clinical characteristics and CNO-related bone pain scores were compared between patients with exclusive nociceptive pain and those with nociceptive pain plus neuropathic and/or nociplastic pain (mixed pain). 31% (95% CI 21-41) of patients classified as likely having neuropathic pain according to PAIN-detect. 53% (41-64) of patients displayed central sensitization on CSI, 61% (50-72) screened positive for fibromyalgia on FiRST and 14% (7-23) of patients fulfilled the AAPT criteria, all indicative of nociplastic pain. Mixed pain was associated with longer diagnostic delay (mean difference 2.8 years, 95% CI 0.4-5.2, p = 0.023), lower educational level (72% versus 20%, p < 0.001), and opioid use (37% versus 13%, p = 0.036). Despite comparable disease severity and extent, patients with mixed pain reported significantly higher CNO-related bone pain scores. This study demonstrates the high prevalence of mixed pain in adult CNO, in which neuropathic and nociplastic pain exist alongside nociceptive inflammatory bone pain. Disease burden in CNO may extend beyond inflammatory activity, highlighting the need for a multifaceted management approach.

Environmental enrichment reverses proulcerogenic action of social isolation on the gastric mucosa and positively influences pain sensitivity and work capacity.

The aim of the study was to investigate the effects of rat housing conditions-standard conditions, social isolation, environmental enrichment-and the subsequent reversal of these conditions on the vulnerability of the gastric mucosa to ulcerogenic stimuli, somatic pain sensitivity, and treadmill work capacity. Rats, aged 30 days, were placed in standard conditions (SC), social isolation (Is), and environmental enrichment (EE) for 4 weeks. Then half of each group underwent a reversal of housing conditions: SC rats were moved to Is, Is rats were placed in EE, EE rats were moved to Is, for 2 weeks. The other half served as a control with no change in their initial housing. Two weeks after the reversal, vulnerability of the gastric mucosa to ulcerogenic action of indomethacin (IM, 35 mg/kg, sc), somatic pain sensitivity (hot plate test), and work capacity (measured by the running distance on a treadmill) were assessed in control and reversed groups. Social isolation induced a proulcerogenic effect, increasing IM-induced gastric erosions, which was effectively reversed when rats were transferred to an environmental enrichment. Conversely, transferring rats from an environmental enrichment to social isolation exacerbated ulcerogenic action of IM. Somatic pain sensitivity and treadmill work capacity were also influenced by housing conditions, with environmental enrichment showing positive effects. The present findings show that social isolation of rats induces a proulcerogenic effect. Environmental enrichment reverses proulcerogenic action of social isolation on the gastric mucosa and increases resilience to pain stimuli and treadmill work capacity.

Translation and cross-cultural adaptation of Polish version of Neuropathic Pain Questionnaire (NPQ-PL) and its comparisons with different questionnaires.

AIM OF THE STUDY: The aim of this study was to assess the validity and reliability of the Polish version of the Neuropathic Pain Questionnaire (NPQ-PL), and to compare it to other diagnostic tools. CLINICAL RATIONALE FOR THE STUDY: Neuropathic pain is a burdensome condition, of which the exact prevalence is difficult to estimate. During initial screening, pain questionnaires are helpful in alerting clinicians about the need for further evaluation. MATERIAL AND METHODS: The NPQ-PL has been developed following the guidelines for translation and cultural adaptation. A total of 140 patients with chronic pain (ChP), 90 with neuropathic pain (NP), and 50 with nociceptive pain (NoP), were enrolled into this study. RESULTS: The study group consisted of 60.71% women and 39.29% men; the mean age of patients (standard deviation, SD) was 53.22 years (15.81), and the average NPQ-PL score (SD) was 0.49 (1.27). Statistically significant relationships were found between higher age distribution and greater pain intensity in the NP group compared to the NoP group. There were also significant differences in pain levels between people of different ages, with the predominance in the elderly. Cronbach's alpha coefficient of the whole questionnaire was 0.85 and the intraclass correlation coefficient (ICC) for test-retest reliability was 0.635. Using receiver-operating characteristic (ROC) curve analysis, the area under the curve (AUC) was 0.97 and the best cut-off value was 0.002, which resulted in the highest sensitivity (93.3%) and specificity (96.0%). CONCLUSIONS AND CLINICAL IMPLICATIONS: The NPQ-PL is a valid tool for discriminating between neuropathic and nociceptive pain. It can be used by physicians of various disciplines when assessing patients with ChP of various origins.

Reliability of the Pen-on-Paper Pain Drawing Analysis Using Different Scanning Procedures.

INTRODUCTION: Pen-on-paper pain drawing are an easily administered self-reported measure that enables patients to report the spatial distribution of their pain. The digitalization of pain drawings has facilitated the extraction of quantitative metrics, such as pain extent and location. This study aimed to assess the reliability of pen-on-paper pain drawing analysis conducted by an automated pain-spot recognition algorithm using various scanning procedures. METHODS: One hundred pain drawings, completed by patients experiencing somatic pain, were repeatedly scanned using diverse technologies and devices. Seven datasets were created, enabling reliability assessments including inter-device, inter-scanner, inter-mobile, inter-software, intra- and inter-operator. Subsequently, the automated pain-spot recognition algorithm estimated pain extent and location values for each digitized pain drawing. The relative reliability of pain extent analysis was determined using the intraclass correlation coefficient, while absolute reliability was evaluated through the standard error of measurement and minimum detectable change. The reliability of pain location analysis was computed using the Jaccard similarity index. RESULTS: The reliability analysis of pain extent consistently yielded intraclass correlation coefficient values above 0.90 for all scanning procedures, with standard error of measurement ranging from 0.03% to 0.13% and minimum detectable change from 0.08% to 0.38%. The mean Jaccard index scores across all dataset comparisons exceeded 0.90. CONCLUSIONS: The analysis of pen-on-paper pain drawings demonstrated excellent reliability, suggesting that the automated pain-spot recognition algorithm is unaffected by scanning procedures. These findings support the algorithm's applicability in both research and clinical practice.

Effect of use of NSAIDs or steroids during the acute phase of pain on the incidence of chronic pain: a systematic review and meta-analysis of randomised trials.

BACKGROUND: This study is the first to summarize the evidence on how the use of anti-inflammatory drugs during acute pain has an impact on the development of chronic pain. METHODS: Randomized controlled trials retrieved from nine databases included anti-inflammatory drugs (NSAIDs or steroids) versus non-anti-inflammatory drugs in patients with acute pain and reported the incidence of chronic pain. No specified date, age, sex, or language restrictions. Subgroup analyses were performed according to pain classification, follow-up time, and medication. The GRADE method was used to evaluate quality of evidence. RESULTS: A total of 29 trials (5220 patients) were included. Steroids or NSAIDs did not reduce the incidence of chronic nociceptive pain. Steroid use in acute phase significantly reduced the incidence of chronic neuropathic pain. In subgroup analysis, benefits were observed for methylprednisolone and dexamethasone, with some adverse effects. Steroids or NSAIDs were statistically significant in reducing pain intensity over 1 year, but the effect size was too small, and whether the long-term effect is clinically relevant needs to be further studied. CONCLUSION: Quality of the evidence was low to moderate. No drug can be recommended to prevent chronic nociceptive pain. Injections of steroids (methylprednisolone or dexamethasone) during the acute phase reduce the incidence of chronic neuropathic pain, but most included studies also used local anesthetics. The results are indirect and need to be interpreted with caution. The pooled data effect sizes for pain intensity were small, so the clinical relevance was unclear. Study registration PROSPERO (CRD42022367030).

Opioid analgesics for nociceptive cancer pain: A comprehensive review.

Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the authors evaluated the efficacy and toxicities of opioid analgesics compared with placebo, other opioids, nonopioid analgesics, and nonpharmacologic treatments for background cancer pain (continuous and relatively constant pain present at rest), and breakthrough cancer pain (transient exacerbation of pain despite stable and adequately controlled background pain). They found a paucity of placebo-controlled trials for background cancer pain, although tapentadol or codeine may be more efficacious than placebo (moderate-certainty to low-certainty evidence). Nonsteroidal anti-inflammatory drugs including aspirin, piroxicam, diclofenac, ketorolac, and the antidepressant medicine imipramine, may be at least as efficacious as opioids for moderate-to-severe background cancer pain. For breakthrough cancer pain, oral transmucosal, buccal, sublingual, or intranasal fentanyl preparations were identified as more efficacious than placebo but were more commonly associated with toxicities, including constipation and nausea. Despite being recommended worldwide for the treatment of cancer pain, morphine was generally not superior to other opioids, nor did it have a more favorable toxicity profile. The interpretation of study results, however, was complicated by the heterogeneity in the study populations evaluated. Given the limited quality and quantity of research, there is a need to reappraise the clinical utility of opioids in people with cancer pain, particularly those who are not at the end of life, and to further explore the effects of opioids on immune system function and quality of life in these individuals.

Memory surfacing among veterans with PTSD receiving hyperbaric oxygen therapy.

Introduction: Growing evidence demonstrates that hyperbaric oxygen therapy (HBO2) induces neuroplasticity and can benefit individuals with post-traumatic stress disorder (PTSD). The aim of the current study was to evaluate the rate and pattern of memory surfacing during the course of HBO2 among veterans with combat-related PTSD. Methods: In a post-hoc analysis of a prospective study of the effect of HBO2 on PTSD symptoms in veterans, we evaluated the rate and character of memory surfacing during the course of HBO2 treatment. The treatment consisted of 60 daily 90-minute sessions, at 2 atmospheres absolute (ATA) pressure and 100% oxygen. Results: For 10 (35.7%) of the 28 participants, surfacing of new memories was reported during the HBO2 treatment course. Memories surfaced mainly during the second month of the treatment, at the mean session of 30.5±13.2. For 9 of these 10 participants, prodromal symptoms such as distress, anxiety, or worsening depression were documented; and in four, somatic pain was reported prior to memory surfacing. The pain and distress of memory surfacing resolved over the course of one to 10 days. Discussion: Among individuals with PTSD, the surfacing of new memories, accompanied by emotional distress and somatic pain, is common during HBO2. The surfacing of memories sheds light on the biological effect of HBO2 on the brain sequela of PTSD. It is highly important that in treating patients for any indication, HBO2 medical teams be aware and capable of addressing memory surfacing, particularly in those with a history of trauma.

[Investigation of the effect of ethylmethylhydroxypyridine succinate on the effectiveness of non-steroidal anti-inflammatory drugs for visceral and somatic pain in mice and rats]. / Izuchenie vliyaniya etilmetilgidroksipiridina suktsinata na effektivnost' nesteroidnykh protivovospalitel'nykh preparatov pri vistseral'noi i somaticheskoi boli v eksperimente na myshakh i krysakh.

OBJECTIVE: To study the effect of ethylmethylhydroxypyridine succinate (EMHPS) on the analgesic effect of the non-selective cyclooxygenase (COX) inhibitor diclofenac sodium and the selective COX-2 inhibitor etoricoxib in models of acute visceral and somatic pain and to evaluate the possibility of using EMHPS in combination with COX inhibitors to reduce their doses while maintaining analgesic efficiency. MATERIAL AND METHODS: We studied the effect of EMHPS with a single oral administration on the analgesic effects of non-steroidal anti-inflammatory drugs (NSAIDs): the non-selective COX inhibitor diclofenac sodium and the selective COX-2 inhibitor etoricoxib - on models of acute visceral (vinegar writhing test) and somatic pain (formalin test and mechanical hyperalgesia during inflammation) in an experiment on mice and rats. RESULTS: In a model of acute visceral pain in mice, EMGPS (25-100 mg/kg) does not have a significant effect on its severity, but enhances the analgesic effect of diclofenac sodium (0.5 mg/kg) and etoricoxib (1 mg/kg). In the formalin test in rats, which simulates pain during surgical incisions (trauma), EMGPS (25 mg/kg) increases the severity of the analgesic effect of COX inhibitors (1 mg/kg), primarily by reducing pain in the acute phase caused by the effect of formalin on afferent neurons. In a model of mechanical hyperalgesia in rats caused by exudative inflammation after injection of a carrageenan solution into the paw, EMHPS enhances the effect of diclofenac to a greater extent than etoricoxib. CONCLUSION: The data obtained indicate the feasibility of a clinical study of the use of EMGPS in combination with NSAIDs for visceral and somatic pain in order to assess its ability to increase the therapeutic effect of NSAIDs.

Investigation for Factors Affecting Body Perception Disturbance in Patients with Low Back Pain by Mechanism-Based Classification of Pain: A Cross-Sectional Study.

Background: Central sensitization is a pathophysiological cause of chronic low back pain and is linked with psychosocial factors. The association between central sensitization (CS) and body perception disturbance is currently unclear, and no prior studies have investigated this relationship in patients with acute or subacute low back pain. The objective of this study was to investigate potential factors that influence body perception disturbance using a mechanistic classification of low back pain. Methods: This cross-sectional study was conducted at the time of initial physical therapy in patients with low back pain. During the study period, 169 patients were recruited. Pain intensity, disease duration, disability, CS, and body perception disturbance were evaluated. Patients were divided into three groups according to the pathology of low back pain, and multivariate analysis was used to examine factors affecting body perception disturbance. The dependent variable was Fremantle Back Awareness Questionnaire (FreBAQ); the independent variables were age, gender, BMI, VAS, disease duration, RDQ, and CS Inventory-9 (CSI-9). Results: A total of 117 patients were included in our analysis. According to the mechanistic classification of pain, 66 (56.4%), 36 (30.8%), and 15 (12.8%) patients were categorized as having nociceptive pain (NP), peripheral neuropathic pain (PNP), and CS pain (CSP), respectively. Patients with PNP or CSP were significantly older than those with NP (p < 0.01). FreBAQ and RDQ scores were significantly higher in patients with CSP than those with NP (p < 0.05). The results of multiple regression analyses indicated that CSI-9 scores were significantly associated with FreBAQ (p < 0.01). Conclusion: Patients with CS syndrome and low back pain tend to have higher CSI-9 scores and be older. Body perception disturbance is influenced by CS or CS syndrome, regardless of the stage of low back pain, suggesting that patients with chronic low back pain tend to have low body image.

Rapid improvements and subsequent effects in major depressive disorder patients with somatic pain using rTMS combined with sertraline.

This study aims to explore changes in depression and pain for major depressive disorder (MDD) patients with somatic pain after repetitive transcranial magnetic stimulation (rTMS) using the event-related potentials (ERPs) technique. Eighty MDD patients with somatic pain were randomly assigned to drug therapy (DT) and combined therapy (CT) groups. CT group underwent intermittent theta burst stimulation over the left dorsolateral prefrontal cortex (DLPFC) with 800 pulses and 1 Hz over the right DLPFC with 800 pulses, 5 times a week for 3 weeks. All patients were given sertraline at 50-100 mg per day. All subjects were evaluated at baseline and at weeks three and six of therapy using the Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Scale (HAMA), and Numerical Rating Scales (NRS), and the latency and amplitude of P300 and mismatch negativity (MMN) were measured. There were no significant differences in all indices between groups at baseline. At 3 weeks, HAMD subscale scores of Cognitive Impairment and NRS scores were significantly lower in the CT group than in the DT group. At 6 weeks, NRS and HAMD total scores in the CT group decreased significantly in the CT group compared with the DT group, especially for anxiety and pain, and the MMN and P300 latencies and P300 amplitude showed greater improvements. Our findings highlight that rTMS in combination with antidepressants is a rapid method of symptom improvement in patients with somatic pain with MDD and is helpful for cognitive impairment and anxiety.

The Ca2+ channel ORAI1 is a regulator of oral cancer growth and nociceptive pain.

Oral cancer causes pain associated with cancer progression. We report here that the function of the Ca2+ channel ORAI1 is an important regulator of oral cancer pain. ORAI1 was highly expressed in tumor samples from patients with oral cancer, and ORAI1 activation caused sustained Ca2+ influx in human oral cancer cells. RNA-seq analysis showed that ORAI1 regulated many genes encoding oral cancer markers such as metalloproteases (MMPs) and pain modulators. Compared with control cells, oral cancer cells lacking ORAI1 formed smaller tumors that elicited decreased allodynia when inoculated into mouse paws. Exposure of trigeminal ganglia neurons to MMP1 evoked an increase in action potentials. These data demonstrate an important role of ORAI1 in oral cancer progression and pain, potentially by controlling MMP1 abundance.

Experimental traumatic occlusion drives immune changes in trigeminal ganglion.

We previously demonstrated that experimental traumatic occlusion (ETO) induces a long-lasting nociceptive response. These findings were associated with altered neuronal patterns and suggestive satellite glial cell activation. This study aimed to elucidate the activation of satellite glial cells following ETO in the trigeminal ganglion. Moreover, we explored the involvement of resident and infiltrating cells in trigeminal ganglion in ETO. Finally, we investigated the overexpression of purinergic signaling and the CX3CL1/CX3CR1 axis. RT-qPCR and electrophoresis showed overexpression of GFAP in the trigeminal ganglion (TG), and immunohistochemistry corroborated these findings, demonstrating SGCs activation. ELISA reveals enhanced levels of TNF-α and IL-1ß in TG after 28 d of ETO. In trigeminal ganglia, ETO groups improved the release of CX3CL1, and immunohistochemistry showed higher CX3CR1+ -immunoreactive cells in ETO groups. Immunohistochemistry and electrophoresis of the P2X7 receptor were found in ETO groups. The mRNA levels of IBA1 are upregulated in the 0.7-mm ETO group, while immunohistochemistry showed higher IBA1+ -immunoreactive cells in both ETO groups. The expression of CD68 by electrophoresis and immunohistochemistry was observed in the ETO groups. For last, ELISA revealed increased levels of IL-6, IL-12, and CCL2 in the TG of ETO groups. Furthermore, the mRNA expression revealed augmented transcription factors and cytokines associated with lymphocyte activation, such as RORγt, IL-17, Tbet, IFNγ, FOXP3, and IL-10. The findings of this study suggested that ETO activates SGCs in TG, and purinergic signaling and CX3CL1/CX3CR1 axis were upregulated. We uncovered the involvement of a distinct subtype of macrophages, named sensory neuron-associated macrophage activation (sNMAs), and detected an expanded number of infiltrated macrophages onto TG. These findings indicate that ETO induces chronic/persistent immune response.

Parkinson's Disease-related Pains are Not Equal: Clinical, Somatosensory and Cortical Excitability Findings in Individuals With Nociceptive Pain.

Chronic pain is a frequent and burdensome nonmotor symptom of Parkinson's disease (PD). PD-related chronic pain can be classified as nociceptive, neuropathic, or nociplastic, the former being the most frequent subtype. However, differences in neurophysiologic profiles between these pain subtypes, and their potential prognostic and therapeutic implications have not been explored yet. This is a cross-sectional study on patients with PD (PwP)-related chronic pain (ie, started with or was aggravated by PD). Subjects were assessed for clinical and pain characteristics through questionnaires and underwent quantitative sensory tests and motor corticospinal excitability (CE) evaluations. Data were then compared between individuals with nociceptive and non-nociceptive (ie, neuropathic or nociplastic) pains. Thirty-five patients were included (51.4% male, 55.7 ± 11.0 years old), 20 of which had nociceptive pain. Patients with nociceptive PD-related pain had lower warm detection threshold (WDT, 33.34 ± 1.39 vs 34.34 ± 1.72, P = .019) and mechanical detection threshold (MDT, 2.55 ± 1.54 vs 3.86 ± .97, P = .007) compared to those with non-nociceptive pains. They also presented a higher proportion of low rest motor threshold values than the non-nociceptive pain ones (64.7% vs 26.6%, P = .048). In non-nociceptive pain patients, there was a negative correlation between WDT and non-motor symptoms scores (r = -.612, P = .045) and a positive correlation between MDT and average pain intensity (r = .629, P = .038), along with neuropathic pain symptom scores (r = .604, P = .049). It is possible to conclude that PD-related chronic pain subtypes have distinctive somatosensory and CE profiles. These preliminary data may help better frame previous contradictory findings in PwP and may have implications for future trial designs aiming at developing individually-tailored therapies. PERSPECTIVE: This work showed that PwP-related nociceptive chronic pain may have distinctive somatosensory and CE profiles than those with non-nociceptive pain subtypes. These data may help shed light on previous contradictory findings in PwP and guide future trials aiming at developing individually-tailored management strategies.

Serum Biomarkers of Nociceptive and Neuropathic Pain in Chronic Pancreatitis.

Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to CP-related pain, which makes successful treatment difficult. The identification of biomarkers for subtypes of pain could provide viable targets for nonopioid interventions and the development of mechanistic approaches to pain management in CP. Nineteen inflammation- and nociception-associated proteins were measured in serum collected from 358 subjects with definite CP enrolled in PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, a prospective observational study of pancreatitis in US adult subjects. First, serum levels of putative biomarkers were compared between CP subjects with and without pain. Only platelet-derived growth factor B (PDGF-B) stood out, with levels significantly higher in the CP pain group as compared to subjects with no pain. Subjects with pain were then stratified into 4 pain subtypes (Neuropathic, Nociceptive, Mixed, and Unclassified). A comparison of putative biomarker concentration among 5 groups (no pain and 4 pain subtypes) identified unique proteins that were correlated with pain subtypes. Serum transforming growth factor beta 1 (TGFß1) level was significantly higher in the Nociceptive pain group compared to the No pain group, suggesting that TGFß1 may be a biomarker for nociceptive pain. The Neuropathic pain only group was too small to detect statistical differences. However, glycoprotein 130 (GP130), a coreceptor for interleukin 6, was significantly higher in the Mixed pain group compared to the groups lacking a neuropathic pain component. These data suggest that GP130 may be a biomarker for neuropathic pain in CP. PERSPECTIVE: Serum TGFß1 and GP130 may be biomarkers for nociceptive and neuropathic CP pain, respectively. Preclinical data suggest inhibiting TGFß1 or GP130 reduces CP pain in rodent models, indicating that additional translational and clinical studies may be warranted to develop a precision medicine approach to the management of pain in CP.

Pain in Parkinson disease: mechanistic substrates, main classification systems, and how to make sense out of them.

ABSTRACT: Parkinson disease (PD) affects up to 2% of the general population older than 65 years and is a major cause of functional loss. Chronic pain is a common nonmotor symptom that affects up to 80% of patients with (Pw) PD both in prodromal phases and during the subsequent stages of the disease, negatively affecting patient's quality of life and function. Pain in PwPD is rather heterogeneous and may occur because of different mechanisms. Targeting motor symptoms by dopamine replacement or with neuromodulatory approaches may only partially control PD-related pain. Pain in general has been classified in PwPD according to the motor signs, pain dimensions, or pain subtypes. Recently, a new classification framework focusing on chronic pain was introduced to group different types of PD pains according to mechanistic descriptors: nociceptive, neuropathic, or neither nociceptive nor neuropathic. This is also in line with the International Classification of Disease-11 , which acknowledges the possibility of chronic secondary musculoskeletal or nociceptive pain due to disease of the CNS. In this narrative review and opinion article, a group of basic and clinical scientists revise the mechanism of pain in PD and the challenges faced when classifying it as a stepping stone to discuss an integrative view of the current classification approaches and how clinical practice can be influenced by them. Knowledge gaps to be tackled by coming classification and therapeutic efforts are presented, as well as a potential framework to address them in a patient-oriented manner.

P2Y12 receptor involved in the development of chronic nociceptive pain as a sensory information mediator.

Direct or indirect damage to the nervous system (such as inflammation or tumor invasion) can lead to dysfunction and pain. The generation of pain is mainly reflected in the activation of glial cells and the abnormal discharge of sensory neurons, which transmit stronger sensory information to the center. P2Y12 receptor plays important roles in physiological and pathophysiological processes including inflammation and pain. P2Y12 receptor involved in the occurrence of pain as a sensory information mediator, which enhances the activation of microglia and the synaptic plasticity of primary sensory neurons, and reaches the higher center through the ascending conduction pathway (mainly spinothalamic tract) to produce pain. While the application of P2Y12 receptor antagonists (PBS-0739, AR-C69931MX and MRS2359) have better antagonistic activity and produce analgesic pharmacological properties. Therefore, in this article, we discussed the role of the P2Y12 receptor in different chronic pains and its use as a pharmacological target for pain relief.

Experimental Pain Picture System (EPPS): Development and Validation.

Pain-related pictures are useful for studying how individuals respond to pain-related stimulation. Such pictures can occasionally be found in databases for affective pictures. However, a validated database specifically for pain-related pictures is not available yet. In 2 experiments (N = 185 and 103, respectively), we developed and validated the Experimental Pain Pictures System (EPPS). In both experiments, negative valence, arousal, and painfulness ratings were compared between neutral-, sad-, and pain-related pictures. The pain-related pictures represented both deep and superficial somatic pain. Across the 2 experiments, pain-related pictures were judged as more negative, arousing, and painful than neutral pictures and more painful than sad pictures. The final EPPS contains 50 pictures of different painful events considered moderately to highly painful by participants. The EPPS is a valuable tool for studying pain-related responses, as it gives researchers a choice among many validated pictures depicting different types of pain, increasing the comparability between studies. PERSPECTIVE: This article presents the validation of the experimental pain pictures system, which consists of a set of pain-related pictures. The experimental pain pictures system is composed of pictures depicting different types of pain. Participants rated all the pictures as being negative, arousing, and painful.

Pharmacologic Management of Cancer-Related Pain in Pregnant Patients.

Despite being an essential part of whole-person care, patients with cancer often experience complex and under-treated pain. Managing cancer-related pain in patients who are also pregnant compounds the challenge for adequate pain management, as studies have largely excluded this population. Therapy for pain management should be guided by the cause and mechanism of pain. The objective of this review is to provide clinicians with an understanding of pain experienced by pregnant patients with cancer and medications that may be used to help manage cancer-related pain. Nociceptive pain results from damage to somatic or visceral tissues that may be directly caused by cancer. This type of pain can be managed in pregnant patients using acetaminophen and/or nonsteroidal antiinflammatory drugs as first-line agents. In nociceptive pain not managed by non-opioid analgesics, buprenorphine is recommended for those requiring chronic opioids to help manage their pain. Neuropathic pain that results from damage to the peripheral or central nervous system may also be directly caused by cancer, particularly chemotherapy. In pregnant patients, duloxetine and gabapentin should be considered first. Venlafaxine, pregabalin, tricyclic antidepressants, and sodium channel blockers should be avoided, if possible. Nociplastic pain is not directly caused by cancer but may be caused by ongoing peripheral nociceptive input or a condition that predates the cancer diagnosis. Duloxetine and gabapentin are reasonable agents to consider for treatment of nociceptive pain in pregnant patients. Cyclobenzaprine may also be helpful for nociplastic pain.