The journal of pain : official journal of the American Pain Society
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Morphine and fentanyl produce antinociception in part by binding to mu-opioid receptors in the periaqueductal gray (PAG). The present study tested the hypothesis that the PAG also contributes to the antinociceptive effects of other commonly used opioids (oxycodone, methadone, and buprenorphine). Microinjection of high doses of oxycodone (32-188 μg/.4 μL) into the ventrolateral PAG of the rat produced a dose-dependent increase in hot plate latency. This antinociception was evident within 5 minutes and nearly gone by 30 minutes. In contrast, no antinociception was evident following microinjection of methadone or buprenorphine into the ventrolateral PAG despite use of a wide range of doses and test times. Antinociception was evident following subsequent microinjection of morphine into the same injection sites or following systemic administration of buprenorphine, demonstrating that the injections sites and drugs could support antinociception. Antinociception to systemic, but not PAG, administration of buprenorphine occurred in both male and female rats. These and previous data demonstrate that the mu-opioid receptor signaling pathway for antinociception in the PAG is selectively activated by some commonly used opioids (eg, morphine, fentanyl, and oxycodone) but not others (eg, methadone or buprenorphine). The fact that methadone and buprenorphine produce antinociception following systemic administration demonstrates that mu-opioid receptor signaling varies depending on location in the nervous system. ⋯ This study demonstrates that the PAG contributes to the antinociceptive effects of some commonly used opioids (morphine, fentanyl, and oxycodone) but not others (methadone or buprenorphine). Such functional selectivity in PAG-mediated opioid antinociception helps explain why the analgesic profile of opioids is so variable.
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Review Meta Analysis
Is tactile acuity altered in people with chronic pain? a systematic review and meta-analysis.
Impaired tactile acuity in people with chronic pain conditions has been suggested to reflect altered cortical representation of the painful body part, and treatments that aim to improve tactile acuity in these conditions have shown clinical benefit. Whether abnormalities in tactile acuity are a consistent feature of chronic pain remains largely unknown. The aim of this review was to systematically evaluate the literature and use meta-analysis to establish whether tactile acuity is altered in people with chronic non-neuropathic pain. We systematically searched the literature for studies that investigated tactile acuity in people with chronic non-neuropathic pain and compared it to an appropriate control group. Sixteen studies, reporting data from 5 chronic pain conditions, were included. Data were available for 18 chronic pain populations (n = 484) and 15 control populations (n = 378). Our results suggest that tactile acuity is diminished in arthritis, complex regional pain syndrome, and chronic low back pain but not in burning mouth syndrome. The strength of the available evidence is weakened by somewhat inconsistent results and the high risk of bias observed in all of the included studies. ⋯ This systematic review synthesizes the evidence for tactile acuity deficits in people with chronic non-neuropathic pain. The findings suggest that tactile acuity deficits may be characteristic of chronic pain. That tactile acuity training may benefit those with chronic pain disorders suggests that clinical trials may be warranted.
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Military personnel returning from conflicts in Iraq and Afghanistan often endorse pain and posttraumatic stress disorder (PTSD) symptoms, either separately or concurrently. Associations between pain and PTSD symptoms may be further complicated by blast exposure from explosive munitions. Although many studies have reported on the prevalence and disability associated with polytraumatic injuries following combat, less is known about symptom maintenance over time. Accordingly, this study examined longitudinal interactive models of co-occurring pain and PTSD symptoms in a sample of 209 military personnel (mean age = 27.4 years, standard deviation = 7.6) who experienced combat-related blast exposure. Autoregressive cross-lagged analysis examined longitudinal associations between self-reported pain and PTSD symptoms over a 1-year period. The best-fitting covariate model indicated that pain and PTSD were significantly associated with one another across all assessment periods, χ² (3) = 3.66, P = .30, Tucker-Lewis index = .98, comparative fit index = 1.00, root mean squared error of approximation = .03. PTSD symptoms had a particularly strong influence on subsequent pain symptoms. The relationship between pain and PTSD symptoms is related to older age, race, and traumatic brain injury characteristics. Results further the understanding of complex injuries among military personnel and highlight the need for comprehensive assessment and rehabilitation efforts addressing the interdependence of pain and co-occurring mental health conditions. ⋯ This longitudinal study demonstrates that pain and PTSD symptoms strongly influence one another and interact across time. These findings have the potential to inform the integrative assessment and treatment of military personnel with polytrauma injuries and who are at risk for persistent deployment-related disorders.
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Comparative Study
Test-retest reliability of pain-related brain activity in healthy controls undergoing experimental thermal pain.
Although functional magnetic resonance imaging (fMRI) has been proposed as a method to elucidate pain-related biomarkers, little information exists related to psychometric properties of fMRI findings. This knowledge is essential for potential translation of this technology to clinical settings. The purpose of this study was to assess the test-retest reliability of pain-related brain activity and how it compares to the reliability of self-report. Twenty-two healthy controls (mean age = 22.6 years, standard deviation = 2.9) underwent 3 runs of an fMRI paradigm that used thermal stimuli to elicit experimental pain. Functional MRI summary statistics related to brain activity during thermal stimulation periods were extracted from bilateral anterior cingulate cortices and anterior insula. Intraclass correlations (ICCs) were conducted on these summary statistics and generally showed "good" test-retest reliability in all regions of interest (ICC range = .32-.88; mean = .71); however, these results did not surpass ICC values from pain ratings, which fell within the "excellent" range (ICC range = .93-.96; mean = .94). Findings suggest that fMRI is a valuable tool for measuring pain mechanisms but did not show an adequate level of test-retest reliability for fMRI to potentially act as a surrogate for individuals' self-report of pain. ⋯ This study is one of the first reports to demonstrate the test-retest reliability of fMRI findings related to pain processing and provides a comparison to the reliability of subjective reports of pain. This information is essential for determining whether fMRI technology should be potentially translated for clinical use.