The journal of pain : official journal of the American Pain Society
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There is uncertainty about sex differences in exercise-induced muscle pain and muscle damage due to several methodological weaknesses in the literature. This investigation tested the hypothesis that higher levels of exercise-induced muscle pain and muscle damage indicators would be found in women than men when several methodological improvements were executed in the same study. Participants (N = 33; 42% women) with an average age of 23 years (SD = 2.82) consented to participate. After a familiarization session, participants visited the laboratory before and across 4 days after eccentric exercise was completed to induce arm muscle pain and muscle damage. Our primary outcomes were arm pain ratings and pressure pain thresholds. However, we also measured the following indicators of muscle damage: arm girth; resting elbow extension; isometric elbow flexor strength; myoglobin (Mb); tumor necrosis factor (TNFa); interleukin 1beta (IL1b); and total nitric oxide (NO). Temporary induction of muscle damage was indicated by changes in all outcome measures except TNFa and IL1b. In contrast to our hypotheses, women reported moderately lower and less frequent muscle pain than men. Also, women's arm girth and Mb levels increased moderately less than men's, but the differences were not significant. Few large sex differences were detected. ⋯ Lower muscle pain among women than men was detected with corresponding, but nonsignificant sex differences in other muscle damage indicators. Methodological advances may have improved alignment of these results with the nonhuman animal findings. This line of research continues to show exceptions to the generalization that women experience greater pain than men.
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Acupuncture is a form of Eastern medicine that has been practiced for centuries. Despite its long history and worldwide application, the biological mechanisms of acupuncture in relieving pain have been poorly defined. Recent studies in mice, however, demonstrate that acupuncture triggers increases in interstitial adenosine, which reduces the severity of chronic pain through adenosine A1 receptors, suggesting that adenosine-mediated antinociception contributes to the clinical benefits of acupuncture. We asked here whether acupuncture in human subjects is also linked to a local increase in interstitial adenosine concentration. We collected microdialysis samples of interstitial fluid before, during, and after delivering 30 minutes of conventional acupuncture in the Zusanli point in human subjects. The interstitial adenosine concentration increased significantly during acupuncture and remained elevated for 30 minutes after the acupuncture. Acupuncture-mediated adenosine release was not observed if acupuncture was not delivered in the Zusanli point or if the acupuncture needle was inserted, but not rotated. This study strengthens the role of adenosine in acupuncture-mediated antinociception by directly providing such evidence in humans. ⋯ This article presents further evidence of the role of adenosine in acupuncture-mediated antinociception by demonstrating that local adenosine concentrations increase in the acupoint in human subjects receiving traditional acupuncture.
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Alpha-7 nicotinic acetylcholine receptor (α7 nAChR) agonists attenuate pain and inflammation in preclinical models. This study tested whether systemic delivery of an α7 nAChR agonist attenuates neuropathic pain and associated immune-mediated pro-inflammation. Hind paw response thresholds to mechanical stimuli in male Sprague Dawley rats were assessed before and after sciatic chronic constriction injury (CCI) or sham surgery. Osmotic mini-pumps containing TC-7020, an α7 nAChR selective agonist, were implanted 10 to 14 days after surgery. TC-7020 (1, 3, and 10 mg/kg/d; s.c.) significantly attenuated CCI-induced allodynia, which lasted through 2 weeks of test compound administration. Spinal cords were collected after 2 weeks and processed for microglial and astrocyte activation markers within the ipsilateral L4-L6 dorsal horn. In addition, ipsilateral L4-5 dorsal root ganglia (DRGs) were processed for neuronal injury and satellite cell activation markers. CCI-induced central glial cell activation markers were not suppressed by TC-7020, even though TC-7020 is mildly blood-brain barrier permeable. However, TC-7020 downregulated the integrated density of activation transcription factor 3 (ATF3) but not the number of ATF positive cells. TC-7020 also downregulated phosphorylated extracellular signal kinase (p-ERK) and satellite cell activation in the CCI-affected DRGs. Therefore, systemic α7 nAChR agonist may be effective in treating neuropathic pain via reducing neuronal injury and immune cells activation occurring in the periphery. ⋯ These studies demonstrated that TC-7020, an alpha7 nicotinic acetylcholine receptor agonist with partial blood-brain barrier permeability, reversed neuropathic pain in rats, likely via attenuation of inflammation in the DRG and/or the site of sciatic injury.