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Chronic diseases and pain exacerbate depressive symptom in Syria. Limited research on hospital-induced depressive symptom among Syrian patients with chronic diseases warrants further study. A cross-sectional study in four Damascus hospitals revealed high rates of pain and depressive symptom. This study aims to investigate the prevalence and severity of chronic pain and hospital-induced depressive symptom in Syrian patients, as well as the relationship between pain, depressive symptom, and medication behavior. This study analyzes the impact of pain, hospitalization, and medication on patients with chronic diseases. The four Damascus hospitals included 453 patients from various departments. Data were collected through structured interviews and internationally recognized scales such as the PSEQ, HADS, and MMAS. These findings offer insights into pain management and psychological well-being, with implications for patient care and support strategies. The study involved 453 patients with chronic diseases, with gender distribution showing 46.6% females and 53.4% males. The age range was from 7 to 87 years, with an average of 46.87 years. Chi-square tests revealed a significant connection between gender and HADS-A scores, where 48.3% of females had abnormalities (χ2 (1, N = 453) = 7.125, p = 0.028). Marital status was significantly associated with anxiety and depressive symptom levels, particularly among widowed and divorced patients. Employment status, education, and comorbidity were linked to abnormal HADS-A scores, while education level showed a positive correlation with HADS-D scores. ANOVA tests showed significant differences in MMAS scores across income groups (F (3, 449) = 3.167, p = 0.024), with a notable difference between low-income and lower-middle-income groups (mean difference = 0.389, p = 0.031. Chronic pain and HID are prevalent among Syrian patients with chronic diseases and influenced by socio-demographic factors. Personalized interventions are needed to address psychological symptoms and medication behavior.

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BACKGROUND: Implementing guidelines for chronic opioid management during a clinic merger posed significant challenges. Our aim was to increase the percentage of chronic pain evaluations and urine toxicology tests in patients on chronic opioid therapy from the baseline rate of less than 20% to 50% within 1 year at an academic, primary care clinic. METHODS: We applied the Define, Measure, Analyze, Improve, Control (DMAIC) approach of Lean Six Sigma for this quality improvement (QI) project. The QI tools included the creation of stakeholder mapping, root cause analysis, process flow mapping and a driver diagram. Lack of patient and provider education emerged as a significant barrier. The outcome measures were percentage of chronic pain evaluations and urine drug toxicology with an increase in controlled substance agreement completion rates as our process measures. Major interventions included patient and provider education, leveraging health information technology, care coordination and implementing new clinic protocols. Data analysis was performed by monthly run charts. Descriptive statistics were used to summarise clinical variables, while χ2 analyses were employed to determine statistically significant differences between preintervention and postintervention measures. RESULTS: We observed an increase in completion rates of clinic visits for chronic pain, rising from 19.0% to 51.9% (p<0.001). During study period, we observed a steady increase in chronic pain evaluations with a median of 4.5. Urine toxicology completion rates increased from 19.9% to 65.8% (p<0.001) during the preintervention and postintervention periods. We observed variable changes in urine toxicology rates with a median of 5.19. Furthermore, we observed an increase in controlled substance agreement completion rates, increasing to 50% from the baseline rate of <10%. CONCLUSIONS: Education to patients and providers, shared decision-making using a patient-centred approach, enhancement of health information technology and system-based interventions in clinic protocols and workflows contributed to the success of this QI project. The DMAIC approach may facilitate the implementation of practice guidelines for chronic opioid therapy and enhance providers' opioid prescribing practices.

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BACKGROUND: Patients with chronic pain on opioids frequently experience loneliness, which is associated with poorer health outcomes and higher risk for opioid misuse and opioid use disorder. Given that almost half of opioids are prescribed in primary care, a critical need exists for the development and testing of interventions to reduce loneliness in primary care patients at risk for opioid misuse. Cognitive behavioral therapy and social prescribing have been shown to be efficacious in reducing loneliness and improving outcomes in other populations but have not been tested in patients at risk for substance use disorder. The overall objective of our study is to reduce opioid misuse and opioid use disorder by addressing loneliness in patients on long-term opioid therapy in real-world primary care settings. METHODS: We will conduct a 3-arm pragmatic, randomized controlled trial to compare the effectiveness of two group-based, telehealth-delivered interventions with treatment as usual: (1) cognitive behavioral therapy to address maladaptive thought patterns and behaviors around social connection and (2) a social prescribing intervention to connect participants with social opportunities and develop supportive social networks. Our primary outcome is loneliness as measured by the UCLA Loneliness Scale and our dependent secondary outcome is opioid misuse as measured by the Common Opioid Misuse Measure. We will recruit 102 patients on long-term opioid therapy who screen positive for loneliness from 2 health care systems in Washington State. Implementation outcomes will be assessed using the RE-AIM framework. DISCUSSION: Our study is innovative because we are targeting loneliness, an under-addressed but critical social risk factor that may prevent opioid misuse and use disorder in the setting where most patients are receiving their opioid prescriptions for chronic pain. If successful, the project will have a positive impact in reducing loneliness, reducing opioid misuse, improving function and preventing substance use disorder. TRIAL REGISTRATION: NCT06285032, issue date: February 28, 2024, original.

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Background: Available therapeutic options are currently limited by their modest efficacy. As a result, novel pharmacotherapeutic treatments with different mechanisms have recently attracted empirical attention. Magnesium, a divalent cation, is postulated to provide analgesic and anti-nociceptive effect through its action at the N-methyl-D-aspartate (NMDA) receptor. Objective: Considering the evidence surrounding magnesium's potential as a therapeutic modality for chronic pain, we conducted a narrative review on the evidence of magnesium's therapeutic effects in chronic pain. Methods: A review of the PubMed, and Google scholar databases was undertaken in May 2022 to identify completed studies that investigated the effectiveness of magnesium in the treatment of chronic pain from database inception to May 2022. Results: A total of 33 studies were included in the narrative review, out of which 26 were randomized controlled trials. Findings on available studies suggest that intravenous infusion of magnesium is an emerging and promising option that may alleviate pain in some clinical populations. Our narrative synthesis showed that evidence for intravenous magnesium is currently equivocal for a variety of chronic pain syndrome. Findings indicate that evidence for efficacy is poor or equivocal for: CRPS, neuropathic pain, chronic low back pain, and migraine prophylaxis. However, there is good evidence supporting the efficacy of intravenous magnesium for treating renal colic pain and pelvic pain related to endometriosis. Conclusion: Magnesium may be a promising pharmacologic solution for chronic pain. Future investigation is warranted on elucidating the neurobiological mechanisms of magnesium in attenuating pain signaling pathways.

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Importance: Chronic back pain (CBP) is a leading cause of disability. Placebo treatments often provide as much pain relief as bona fide treatments, such as steroid injections. Open-label (honestly prescribed) placebos (OLPs) may relieve CBP without deception, but OLP mechanisms remain poorly understood. Objective: To investigate the long-term efficacy and neurobiological mechanisms of OLP for CBP. Design, Setting, and Participants: A randomized clinical trial of CBP with longitudinal functional magnetic resonance imaging (MRI) comparing OLP with usual care, with 1-year follow-up, was conducted in a university research setting and a community orthopedic clinic. Participants were individuals aged 21 to 70 years with CBP. The trial was conducted from November 2017 to August 2018, with 1-year follow-up completed by November 2019. Data analysis was performed from April 2020 to May 2024. The primary analysis was conducted on an intention-to-treat sample. Interventions: Participants randomized to OLP received a 1-time subcutaneous lumbar saline injection presented as placebo accompanied by information about the power of placebo to relieve pain, alongside their ongoing care. Usual care participants continued their ongoing care. Main Outcomes and Measures: The primary outcome was pain intensity (0-10, with 0 indicating no pain and 10 the most intense) at 1 month posttreatment. Secondary outcomes included pain interference, depression, anxiety, anger, and sleep quality. Functional MRI was performed before and after treatment during evoked and spontaneous back pain. Results: A total of 101 adults (52 [51.4%] females; mean [SD] age, 40.4 [15.4] years) with moderate severity CBP (mean [SD], 4.10 [1.25] intensity; duration, 9.7 [8.5] years) were enrolled. Compared with usual care, OLP reduced CBP intensity posttreatment (relative reduction, 0.61; Hedges g = 0.45; 95% CI, -0.89 to 0.04; P = .02). Through 1-year follow-up, pain relief did not persist, although significant benefits were observed for depression, anger, anxiety, and sleep disruption (Hedges g = 0.3-0.5; all P < .03). Brain responses to evoked back pain for OLP vs usual care increased in rostral anterior cingulate and ventromedial prefrontal cortex and decreased in somatomotor cortices and thalamus. During spontaneous pain, functional connectivity analyses identified OLP vs usual care increases in ventromedial prefrontal cortex connectivity to the rostral ventral medulla, a pain-modulatory brainstem nucleus. No adverse effects of treatment were reported by participants. Conclusions and Relevance: In this randomized clinical trial of OLP vs usual care, a single nondeceptive placebo injection reduced CBP intensity for 1 month posttreatment and provided benefits lasting for at least 1 year posttreatment. Brain mechanisms of OLP in a clinical population overlap with those of deceptive placebos in healthy volunteers, including engagement of prefrontal-brainstem pain modulatory pathways. Trial Registration: ClinicalTrials.gov Identifier: NCT03294148.

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BACKGROUND: Whether regional anesthesia impacts the development of chronic postsurgical pain is currently debateable, and few studies have evaluated an effect on prolonged opioid use. We sought to systematically review the effect of regional anesthesia for adults undergoing noncardiac elective surgery on these outcomes. METHODS: A systematic search was conducted in MEDLINE, EMBASE, CENTRAL, and CINHAL for randomized controlled trials (from inception to April 2022) of adult patients undergoing elective noncardiac surgeries that evaluated any regional technique and included one of our primary outcomes: (1) prolonged opioid use after surgery (continued opioid use ≥2 months postsurgery) and (2) chronic postsurgical pain (pain ≥3 months postsurgery). We conducted a random-effects meta-analysis on the specified outcomes and used the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach to rate the quality of evidence. RESULTS: Thirty-seven studies were included in the review. Pooled estimates indicated that regional anesthesia had a significant effect on reducing prolonged opioid use (relative risk [RR] 0.48, 95% CI, 0.24-0.96, P = .04, I 2 0%, 5 trials, n = 348 patients, GRADE low quality). Pooled estimates for chronic pain also indicated a significant effect favoring regional anesthesia at 3 (RR, 0.74, 95% CI, 0.59-0.93, P = .01, I 2 77%, 15 trials, n = 1489 patients, GRADE moderate quality) and 6 months (RR, 0.72, 95% CI, 0.61-0.85, P < .001, I 2 54%, 19 trials, n = 3457 patients, GRADE moderate quality) after surgery. No effect was found in the pooled analysis at 12 months postsurgery (RR, 0.44, 95% CI, 0.16-1.17, P = .10). CONCLUSIONS: The results of this study suggest that regional anesthesia potentially reduces chronic postsurgical pain up to 6 months after surgery. Our findings also suggest a potential decrease in the development of persistent opioid use.

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Transient receptor potential (TRP) channels, first identified in Drosophila in 1969, are multifunctional ion channels expressed in various cell types. Structurally, TRP channels consist of six membrane segments and are classified into seven subfamilies. Transient receptor potential ankyrin 1 (TRPA1), the first member of the TRPA family, is a calcium ion affinity non-selective cation channel involved in sensory transduction and responds to odors, tastes, and chemicals. It also regulates temperature and responses to stimuli. Recent studies have linked TRPA1 to several disorders, including chronic pain, inflammatory diseases, allergies, and respiratory problems, owing to its activation by environmental toxins. Mutations in TRPA1 can affect the sensory nerves and microvasculature, potentially causing nerve pain and vascular problems. Understanding the function of TRPA1 is important for the development of treatments for these diseases. Recent developments in nanomedicines that target various ion channels, including TRPA1, have had a significant impact on disease treatment, providing innovative alternatives to traditional disease treatments by overcoming various adverse effects.

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Pain is an unpleasant sensory and emotional experience. Adequate pain control is often challenging, particularly in patients with chronic pain. Despite advances in pain management, drug addiction, overtreatment, or substance use disorders are not rare. Hence the need for further studies in the field. The substantial progress made over the last decade has revealed genes, signalling pathways, molecules, and neuronal networks in pain control thus opening new clinical perspectives in pain management. In this respect, data on the epigenetic modulation of opioid and cannabinoid receptors, key actors in the modulation of pain, offered new perspectives to preserve the activity of opioid and endocannabinoid systems to increase the analgesic efficacy of opioid- and cannabinoid-based drugs. Similarly, upcoming data on cannabidiol (CBD), a non-psychoactive cannabinoid in the marijuana plant Cannabis sativa, suggests analgesic, anti-inflammatory, antioxidant, anticonvulsivant and ansiolitic effects and supports its potential application in clinical contexts such as cancer, neurodegeneration, and autoimmune diseases but also in health and fitness with potential use in athletes. Hence, in this review article, we summarize the emerging epigenetic modifications of opioid and cannabinoid receptors and focus on CBD as an emerging non-psychoactive cannabinoid in pain management in clinical practice, health, and fitness.

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OBJECTIVE: To examine trends in chronic pain (CP) practice patterns among community-based family physicians (FPs). DESIGN: Population-based descriptive study using health administrative data. SETTING: British Columbia from fiscal years 2008-2009 to 2017-2018. PARTICIPANTS: Patients with an algorithm-defined CP condition and community-based FPs, both registered with the British Columbia Medical Services Plan. MAIN OUTCOME MEASURES: Using British Columbia health administrative data and a CP algorithm adapted from a previous study, the following were compared between fiscal years 2008-2009 and 2017-2018: CP patient volumes, pain-related medication prescriptions, referrals to pain specialists, musculoskeletal imaging requests, and interventional procedures. RESULTS: In the fiscal year 2017-2018, among community-based family physicians (N=4796), an average of 32.5% of their patients had CP. Between 2008-2009 and 2017-2018, the proportion of CP patients per FP who were prescribed long-term opioids increased by an average absolute change of 0.56%; the proportion prescribed long-term neuropathic pain medications increased by 1.1%; and the proportion prescribed long-term nonsteroidal anti-inflammatory drugs decreased by 0.49%. The proportion of musculoskeletal imaging out of all imaging requests made by FPs increased by 2.0%; pain-related referrals increased by 1.73%; there was a 4.6% increase in the proportion of community-based FPs who performed 1 or more pain injections; and 10% more FPs performed 1 or more trigger point injections within a fiscal year. CONCLUSION: Findings show that the work of providing care to patients with CP increased while CP patient volumes per FP decreased. Workforce planning for community-based FPs should consider these increased demands and ensure FPs are adequately supported to provide CP care.

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INTRODUCTION: Total knee arthroplasty (TKA) is accompanied by severe postoperative pain, which is reported to be an important cause of chronic pain. Ultrasound-guided adductor canal block (ACB) combined with infiltration between the popliteal artery and posterior capsular of the knee (IPACK) has been proven to have a better effect on relieving acute pain after TKA. However, whether it has a significant effect on the incidence of chronic pain after TKA has not been reported. This trial was designed to investigate the effect of ultrasound-guided ACB combined with IPACK on the incidence and intensity of chronic pain after TKA. METHODS: In this prospective, randomized, double-blind, placebo-controlled study, 100 subjects scheduled for TKA were randomly (1:1) divided into two groups: the ropivacaine group and the placebo group. Patients in each group received ultrasound-guided ACB + IPACK procedures with 0.25% ropivacaine or equal volume normal saline. All patients received multimodal analgesia. Pain intensity was assessed using the Numerical Rating Scale (NRS). The primary outcome was the incidence of chronic pain at 3 months after TKA by telephone follow-up. In addition, pain intensity in early resting and mobilized states, chronic pain intensity, the time to first rescue analgesia; opioid consumption; CRP and IL-6 after the operation; length of postoperative hospital stay; and cost of hospitalization and postoperative complications; as well as the function of the knee in the early stage after the operation, were recorded. RESULTS: Ninety-one participants were included in the final analysis. At 3 months, the incidence of chronic pain was 30.4% in the ropivacaine group, significantly lower than 51.1% in the placebo group. Compared with the placebo group, the ACB + IPACK with ropivacaine group had significantly lower pain scores at 4 hours, 8 hours, 16 hours, and 24 hours after the operation; increased the knee range of motion at 8 hours and 24 hours after the operation; and a significantly decreased incidence of chronic pain at 3 months after the operation. During the follow-up period, there were no nerve block-related complications in either group. CONCLUSION: In the context of multimodal analgesia protocols, ACB combined with IPACK before surgery decreases the incidence and intensity of chronic pain 3 months after TKA compared with placebo injection. In addition, it reduces the NRS scores, whether at rest or during mobilization, and improves knee function within 24 hours after TKA. TRIAL REGISTRATION: This trial was registered in the China Clinical Trial Center (registration number ChiCTR2200065300) on November 1, 2022.

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OBJECTIVE: Cervical epidural steroid injections (ESIs) can provide effective pain management for patients suffering from chronic neck pain due to various pathological changes of the cervical spine. There are several rare adverse effects reported from interventional pain procedures, including persistent hiccups ("singultus"). Based on a limited number of cases, we propose a modified treatment algorithm for this adverse outcome (Fig. 3). CASE REPORT: Singultus has been documented as an adverse effect of interventional pain procedures, including epidural steroid, facet joint, and sacroiliac joint injections. We describe the case of a general contractor who presented to our clinic with chronic neck pain and central canal stenosis. The patient received an uncomplicated lumbar ESI in the past and was recommended for a cervical interlaminar ESI. After an uneventful C6-C7 interlaminar ESI with dexamethasone, 1% lidocaine, and normal saline the patient developed singultus. Baclofen was sent to his pharmacy, but this was unsuccessful at alleviating his hiccups. The patient was subsequently started on chlorpromazine and found relief from his symptomatology. CONCLUSION: Persistent hiccups after ESI or interventional pain procedures can be treated with conservative measures and non-pharmacologic methods, with escalation to therapy with baclofen, gabapentin, pregabalin, metoclopramide, chlorpromazine, other antipsychotic or antidopaminergic agents, and possible dual or triple therapy if further indicated.

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Fibromyalgia is characterized by chronic widespread pain, fatigue, and sleep disturbances. Recent theories attribute fibromyalgia to central sensitization syndromes, suggesting altered nociceptive processing leads to hyperalgesia and allodynia. Standardized effective treatments are currently lacking. Palmitoylethanolamide and melatonin have shown pain-relieving effects in chronic pain conditions, including fibromyalgia, with excellent safety. Our open-label study assessed the impact of a daily combination of 1200 mg of palmitoylethanolamide and 0.2 mg of melatonin on pain, sleep, and quality of life in fibromyalgia patients. Between June 2023 and March 2024, 50 patients (2016 ACR criteria) were treated and evaluated at baseline, 1 month, 3 months, and 4 months (1 month discontinuation). The assessments included VAS for pain, ISI for insomnia, HAQ for health assessments, and a tender points evaluation. The patients, averaging 54.12 years old with a 3:1 female-to-male ratio, showed significant improvements in VAS, ISI, and HAQ scores relative to their own baselines and a reduction in tender points at 1 and 3 months, which was maintained at 4 months. No adverse events were reported. This study is the first to demonstrate the efficacy of a palmitoylethanolamide and melatonin combination as an adjunct therapy in fibromyalgia, highlighting its potential to reduce pain and improve sleep and quality of life.

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Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6-guided therapy will improve pain control and reduce adverse drug events. However, CYP2D6 is rarely used in clinical practice due in part to the demand for additional clinical trial evidence. Thus, we designed the ADOPT-PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) chronic pain study, a multicenter, pragmatic, randomized controlled clinical trial, to assess the effect of CYP2D6 testing on pain management. The study enrolled 1048 participants who are taking or being considered for treatment with CYP2D6-impacted opioids for their chronic pain. Participants were randomized to receive immediate or delayed (by 6 months) genotyping of CYP2D6 with clinical decision support (CDS). CDS encouraged the providers to follow the CYP2D6-guided trial recommendations. The primary study outcome is the 3-month absolute change in the composite pain intensity score assessed using Patient-Reported Outcomes Measurement Information System (PROMIS) measures. Follow-up will be completed in July 2024. Herein, we describe the design of this trial along with challenges encountered during enrollment.

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The use of Medicinal Cannabis (MC) for treating chronic pain is increasing, globally, yet the definition of problematic MC use remains unclear. Defining problematic use of cannabis in medical and non-medical contexts may be fundamentally different since individuals prescribed MC often experience physical dependence, which do not necessarily imply pathology. We aimed to conceptualize problematic use of MC and develop a brief questionnaire for identifying and quantifying problematic MC use. Content validation used a broad definition of problematic substance use, adapting and compiling an initial list of 36 items from various sources: (a) screening tools for assessing problematic prescription opioid medication use; (b) screening tools for problematic recreational cannabis use and (c) qualitative interviews with MC patients. 390 American self-identified chronic pain patients holding a MC card rated each item from the initial list on a 5-point frequency scale and filled out questionnaires assessing various clinical outcomes. Following initial item titration, a multi-group measurement invariance comparison strategy, using two external indicators: alcohol-related problems and depression, resulted a final eight-item list that met fit quality in a baseline model, presented excellent internal consistency reliability (α = 0.929), and significantly correlated with anxiety and low quality of life. Items in the final list related predominantly to negative consequences of MC use. Problematic use of MC is characterized by negative physiological, social, emotional and functional consequences. The final eight-item list was named the Medicinal Cannabis Negative Consequences Scale (MCNCS), emerging as a brief measure for problematic MC use and demonstrating preliminary reliability and validity, which could aid clinicians and researchers.

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OBJECTIVE: To analyze patient and caregiver narratives addressing experiences related to substance use and substance use disorder (SUD). METHODS: Thirty audio-narratives from the MyPaTH Story Booth archive addressed substance use between 5/20/2016 and 2/24/21. Two coders established an average Cohen's kappa statistics of 0.81 over 16 stories. The primary coder coded and summarized additional narratives and conducted content and thematic analyses. The final analytic sample addressed perspectives of individuals with SUD, caregivers for individuals with SUD and individuals who have used opioids to manage pain. RESULTS: Storytellers' average age was 51, 55 % were female and 85 % were white. Participants with SUD and caregivers described frustration with the current treatment system, reported limited treatment of SUD in medical settings, and noted relying on community-based groups for ongoing care. Individuals with chronic pain felt stigmatized and resented perceived restrictions on pain treatment due to the opioid epidemic. CONCLUSIONS: Unstructured narratives provide insights into the lived experiences of people impacted by SUD. Participants reported struggling with the effects of SUD and failing to find adequate treatment from the medical system. Stories highlight SUD-related stigma. PRACTICE IMPLICATIONS: Understanding patient and caregiver perspectives related to SUD can be a critical step towards developing effective interventions.

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OBJECTIVE: Despite the wide use of ziconotide in the USA for treating refractory cancer- and noncancer-related pain, this agent is little used in Europe, even if licensed by the European Medicines Agency (EMA). The reason could be attributed to the high, fixed starting dose required for ziconotide, as stated in the EMA Summary of Product Characteristics (SmPC). This dosage recommendation is based on the results of pivotal clinical studies of ziconotide, which utilized aggressive titration schedules. Thus, a reappraisal of the available evidence, as well as a reflection on real-life clinical experiences, might be useful to identify practice adjustments to improve the clinical application of ziconotide in the European scenario. In line with this need, this paper reports some clinical experiences of patients with chronic pain treated with ziconotide intrathecal (IT) therapy in Italy, particularly focusing on long-term treatment to further characterize and improve the use of this agent in real practice. Moreover, a literature review of the available data on the effectiveness and safety of IT ziconotide is provided. CASE SERIES: Collected clinical experiences suggested that the use of IT ziconotide represents a valuable option, particularly in cases where other treatments have been ineffective or poorly tolerated. Ziconotide was shown to not cause severe side effects in the long-term treatment, leading to a constant pain relief effect at stable doses, without adverse events that caused therapy interruption. The overall constant ziconotide dosages also suggest the absence of a tolerance effect. In parallel, the evidence in the literature aligns with real-world evidence and further supports the use of IT ziconotide as an important option for the management of chronic pain. CONCLUSIONS: IT ziconotide represents a valuable addition to the armamentarium of pain management strategies, offering hope for improved quality of life for patients suffering from chronic, treatment-resistant pain. Continued research and clinical experience will further elucidate its optimal use and role in comprehensive pain care.

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Neuropeptides, including tachykinins, CGRP, and somatostatin, are localized in a peptidergic subgroup of nociceptive primary afferent neurons. Tachykinins and CGRP are pronociceptive, somatostatin is an antinociceptive mediator. Intensive drug research has been performed to develop tachykinin and CGRP antagonists, and somatostatin agonists as analgesics. CGRP receptor antagonists are efficacious and well-tolerated drugs in migraine. Monoclonal antibodies against CGRP or its receptor are used for the prophylactic treatment of migraine. Tachykinin NK1 receptor antagonists failed as analgesics but are used for chemotherapy-induced nausea and vomiting. New, orally active somatostatin 4 receptor agonists are promising drug candidates for treating various pain conditions.

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