Pain
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Peripheral serotonin (5HT) has been implicated in migraine and temporomandibular pain disorders in humans and animal models and yet the mechanism(s) by which 5HT evokes pain remains unclear. Trigeminal pain can be triggered by activation of the transient receptor potential V1 channel (TRPV1), expressed by a subset of nociceptive trigeminal ganglia (TG) neurons and gated by capsaicin, noxious heat, and other noxious stimuli. As 5HT is released in the periphery during inflammation and evokes thermal hyperalgesia, and TRPV1 is essential for thermal hyperalgesia, we hypothesized that 5HT increases the activity of capsaicin-sensitive trigeminal neurons and that this increase can be attenuated by pharmacologically targeting peripheral 5HT receptors. ⋯ In addition, using in situ hybridization and immunohistochemistry, we detected the colocalization of 5HT(1B), 5HT(1D), 5HT(2A), and 5HT(3A), but not 5HT(2C) mRNA with TRPV1 in TG cells. 5HT pretreatment evoked a significant increase in calcium accumulation in capsaicin-sensitive trigeminal neurons and enhanced capsaicin-evoked CGRP release, but had no significant effect when given alone. Sumatriptan, ketanserin, and granisetron treatment attenuated calcium accumulation and 5HT enhancement of capsaicin-evoked CGRP release. Together these results indicate that 5HT increases the activity of capsaicin-sensitive peripheral nociceptors, which can be attenuated by pharmacologically targeting peripheral 5HT receptors, thereby providing a mechanistic basis for peripheral craniofacial pain therapy.
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Review Meta Analysis Comparative Study
Comparing patients' and clinician-researchers' outcome choice for psychological treatment of chronic pain.
In pain treatment, outcomes are generally defined by researchers and clinicians, predominantly using patient self-report. A large-scale survey of people with chronic pain found a more extensive range of treatment outcomes rated important (Turk et al., "Identifying important outcome domains for chronic pain clinical trials: an IMMPACT survey of people with pain." PAIN 2008;137:276-85) than are conventionally used (Turk et al., "Core outcome domains for chronic pain clinical trials: IMMPACT recommendations." PAIN 2003;106:337-45). We compared outcomes from 60 randomised, controlled trials of cognitive and/or behavioural treatment for persistent pain with the 19 domains rated as most important in the survey. ⋯ Five of the 19 outcomes important to survey respondents were not measured at all, and 8 rarely. There was a positive, although modest, correlation between the methodological quality of trials and their coverage of survey respondents' outcomes. We lack measures in many areas of outcome valued by people with chronic pain, and we need to extend routine measurement of trial outcomes.
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Randomized Controlled Trial Multicenter Study Comparative Study
Efficacy and safety of tanezumab in the treatment of chronic low back pain.
Increased nerve growth factor levels are associated with chronic pain conditions, including chronic low back pain (LBP). This study examined safety and analgesic efficacy of tanezumab, a humanized anti-nerve growth factor antibody, in adults with chronic LBP. Patients received intravenous tanezumab 200 μg/kg plus oral placebo (n=88), intravenous placebo plus oral naproxen 500 mg twice a day (n=88), or intravenous placebo plus oral placebo (n=41). ⋯ Nine patients (4 of whom were tanezumab-treated) discontinued due to AEs. In conclusion, tanezumab resulted in analgesic efficacy that was clinically and statistically superior to placebo and naproxen in patients with chronic LBP. Tanezumab clinical development is on regulatory hold due to AEs in osteoarthritis patients.
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The comorbidity of pain syndromes and trauma-related syndromes has been shown to be high. However, there have been limited data, especially in civilian medical populations, on the role of trauma-related disorders such as posttraumatic stress disorder (PTSD) on chronic pain and pain medication use. We analyzed 647 general hospital patients in primary care and obstetrics and gynecological waiting rooms for the experience of trauma and PTSD-related stress disorders. ⋯ When analyzing the separate PTSD symptom subclusters (re-experiencing, avoidance, and hyperarousal), all symptom clusters were significantly related to pain and pain-related impairment ratings, but only the avoidance cluster was significantly related to prior opioid pain medication use. We conclude that PTSD and trauma-related disorders are common in impoverished medical populations and that their presence should be examined in patients with pain syndromes. Furthermore, these data suggest that PTSD and pain may share a vulnerability pathway, including the endogenous opioid neurotransmission systems.