The journal of pain : official journal of the American Pain Society
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Evidence suggests that the effect of cigarette smoking on chronic pain is stronger in younger than older adults. This case-control study investigated whether age modified an effect of smoking on temporomandibular disorder (TMD) in 299 females aged 18 to 60 years. It also investigated the extent to which this relationship was explained by psychological profile, inflammatory response, and allergy. Cases were defined using the Research Diagnostic Criteria for Temporomandibular Disorders based on clinical examination. Psychological profile was evaluated using standardized instruments. Inflammatory response was evaluated with 11 cytokines isolated in plasma. History of allergy conditions was self-reported. Odds ratios (ORs) for the effect of smoking were calculated using binary logistic regression. Stratified analyses and the likelihood ratio test examined effect modification by smoking. Compared with nonsmokers, ever smokers aged <30 years had higher odds of TMD (OR = 4.14, 95% CI: 1.57, 11.35) than older adults (OR = 1.23, 95% CI: .55, 2.78) (P (effect modification) = .038). Adjustment for psychological profile, cytokines, and history of allergy-like conditions attenuated the effect by 45% to statistical nonsignificance. The main finding was reproduced with secondary analyses of 2 nationally representative surveys of adults conducted in the US and Australia. ⋯ This study showed that smoking was associated with TMD risk in females, but only in young adulthood. It replicated this finding in 2 nationally representative surveys of females in the US and Australia. Findings may alert clinicians to recognize that smoking is a concern for TMD in younger female patients.
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Complex Regional Pain Syndrome (CRPS) is a chronic and often disabling pain disorder. There is evidence demonstrating that neurogenic inflammation and activation of the immune system play a significant role in the pathophysiology of CRPS. This study evaluated the plasma levels of cytokines, chemokines, and their soluble receptors in 148 subjects afflicted with CRPS and in 60 gender- and age-matched healthy controls. Significant changes in plasma cytokines, chemokines, and their soluble receptors were found in subjects with CRPS as compared with healthy controls. For most analytes, these changes resulted from a distinct subset of the CRPS subjects. When the plasma data from the CRPS subjects was subjected to cluster analysis, it revealed 2 clusters within the CRPS population. The category identified as most important for cluster separation by the clustering algorithm was TNFα. Cluster 1 consisted of 64% of CRPS subjects and demonstrated analyte values similar to the healthy control individuals. Cluster 2 consisted of 36% of the CRPS subjects and demonstrated significantly elevated levels of most analytes and in addition, it showed that the increased plasma analyte levels in this cluster were correlated with disease duration and severity. ⋯ The identification of biomarkers that define disease subgroups can be of great value in the design of specific therapies and of great benefit to the design of clinical trials. It may also aid in advancing our understanding of the mechanisms involved in the pathophysiology of CRPS, which may lead to novel treatments for this very severe condition.
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Recent reports suggest deficits in conditioned pain modulation (CPM) and enhanced suprathreshold heat pain response (SHPR) potentially play a role in the development of chronic pain. The purpose of this study was to investigate whether central pain processing was altered in 2 musculoskeletal shoulder pain models. The goals of this study were to determine whether central pain processing: 1) differs between healthy subjects and patients with clinical shoulder pain; 2) changes with induction of exercise-induced muscle pain; and 3) changes 3 months after shoulder surgery. Fifty-eight patients with clinical shoulder pain and 56 age- and sex-matched healthy subjects were included in these analyses. The healthy cohort was examined before inducing EIMP, and 48 and 96 hours later. The clinical cohort was examined before shoulder surgery and 3 months later. CPM did not differ between the cohorts, however; SHPR was elevated for patients with shoulder pain compared to healthy controls. Induction of acute shoulder pain with EIMP resulted in increased shoulder pain intensity but did not change CPM or SHPR. Three months following shoulder surgery, clinical pain intensity decreased but CPM was unchanged from preoperative assessment. In contrast, SHPR was decreased and showed values comparable with healthy controls at 3 months. Therefore, the present study suggests that: 1) clinical shoulder pain is associated with measurable changes in central pain processing; 2) exercise-induced shoulder pain did not affect measures of central pain processing; and 3) elevated SHPR was normalized with shoulder surgery. Collectively our findings support neuroplastic changes in pain modulation were associated with decreases in clinical pain intensity only, and could be detected more readily with thermal stimuli. ⋯ Longitudinal studies involving quantitative sensory testing are rare. In exploring 2 musculoskeletal shoulder pain models (exercise-induced muscle pain and surgical pain), conditioned pain modulation was unchanged from pre- to post-assessment in both models. Suprathreshold heat pain response decreased after shoulder surgery and was comparable to healthy controls, suggesting this measure may be sensitive to decreases in clinical pain intensity.
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The present study examined the role of endogenous noradrenaline on glial and neuronal plasticity in the spinal cord in rats after peripheral nerve injury. An intrathecal injection of dopamine-β-hydroxylase antibody conjugated to saporin (DβH-saporin) completely depleted noradrenergic axons in the spinal cord and also reduced noradrenergic neurons in the locus coeruleus (A6) and A5 noradrenergic nucleus in the brainstem and noradrenergic axons in the paraventricular nucleus of the hypothalamus. DβH-saporin treatment itself did not alter mechanical withdrawal threshold, but enhanced mechanical hypersensitivity and intrathecal clonidine analgesia after L5-L6 spinal nerve ligation. In the spinal dorsal horn of spinal nerve ligation rats, DβH-saporin treatment increased choline acetyltransferase immunoreactivity as well as immunoreactivity in microglia of ionized calcium binding adaptor molecule 1[IBA1] and in astrocytes of glial fibrillary acidic protein, and brain-derived nerve growth factor content. DβH-saporin treatment did not, however, alter the fractional release of acetylcholine from terminals by dexmedetomidine after nerve injury. These results suggest that endogenous tone of noradrenergic fibers is not necessary for the plasticity of α2-adrenoceptor analgesia and glial activation after nerve injury, but might play an inhibitory role on glial activation. ⋯ This study demonstrates that endogenous noradrenaline modulates plasticity of glia and cholinergic neurons in the spinal cord after peripheral nerve injury and hence influences the pathophysiology of spinal cord changes associated with neuropathic pain.
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In this study, we aimed to evaluate the antinociceptive interaction between intrathecally administered amiloride and morphine or clonidine. Using rats chronically implanted with lumbar intrathecal catheters, we examined the ability of intrathecal amiloride, morphine, clonidine, and mixtures of amiloride-morphine and amiloride-clonidine to alter tail-flick latency. To characterize any interactions, isobolographic analysis was performed. The effects of pretreatment with intrathecally administered naloxone or yohimbine were tested. Intrathecal administration of amiloride (25-150 μg), morphine (.25-10 μg), or clonidine (.5-10 μg) alone produced significant dose-dependent antinociception in the tail-flick test. The median effective dose (ED(50)) values for intrathecally administered amiloride, morphine, and clonidine were 120.5 μg, 5.0 μg, and 4.4 μg, respectively. Isobolographic analysis exhibited a synergistic interaction after coadministration of amiloride-morphine and amiloride-clonidine. Intrathecal pretreatment with naloxone (10 μg) completely blocked the antinociceptive effects of morphine and the amiloride-morphine mixture. Intrathecal pretreatment with yohimbine (20 μg) completely blocked the antinociceptive effect of clonidine and antagonized the effect of the amiloride-clonidine mixture. There was no motor dysfunction or significant change in blood pressure or heart rate after the intrathecal administration of amiloride, amiloride-morphine, and amiloride-clonidine. The synergistic effect observed after the coadministration of amiloride and morphine or clonidine suggests a functional interaction among calcium channels, μ-receptors and α(2)-receptors at the spinal cord level of the nociceptive processing system. ⋯ Although intrathecal morphine and clonidine produces pronounced analgesia, antinociceptive doses of intrathecal morphine and clonidine produce several side effects, including hypotension, bradycardia, sedation, and tolerance. This article presents antinociceptive synergistic interaction between amiloride and morphine, amiloride, and clonidine on thermal nociceptive tests in the rat.