Pain
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Comparative Study
Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1.
Clinically, chronic pain and hyperalgesia induced by muscle injury are disabling and difficult to treat. Cellular and molecular mechanisms underlying chronic muscle-induced hyperalgesia are not well understood. For this reason, we developed an animal model where repeated injections of acidic saline into one gastrocnemius muscle produce bilateral, long-lasting mechanical hypersensitivity of the paw (i.e. hyperalgesia) without associated tissue damage. ⋯ These changes in WDR neurons do not occur in ASIC3 knockouts. Thus, activation of ASIC3s on muscle afferents is required for development of mechanical hyperalgesia and central sensitization that normally occurs in response to repeated intramuscular acid. Therefore, interfering with ASIC3 might be of benefit in treatment or prevention of chronic hyperalgesia.
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Comparative Study
Afferent fiber-selective shift in opiate potency following targeted opioid receptor knockdown.
Spinal application of opiates is the cornerstone of potent analgesia. In the present study, opiate analgesia was investigated after cutaneous application of a recombinant herpes simplex virus type-1 (HSV-1) encoding micro-opioid receptor (microOR) cDNA in reverse orientation with respect to the human cytomegalovirus early enhancer-promoter. Hind paw application of this recombinant vector was used in order to attenuate expression of the microOR in primary afferents and determine whether recombinant vector application would differentially affect the antinociceptive effects of the specific microOR agonist, [D-Ala(2),N-MePhe(4),Gly-ol(5)] enkephalin (DAMGO), on behavioral responses mediated by C- and Adelta-thermonociceptors. ⋯ However, cutaneous application of dorsal hind paw surfaces treated with AMOR, but not KHZ, caused a rightward shift in the C-fiber dose-response, thus, indicating a loss of potency of intrathecal DAMGO. Loss or diminution of DAMGO potency during Adelta-fiber-mediated responses was not observed. These immunohistochemistry and behavioral results of novel, recombinant HSV-1 vector microOR 'knock-down' in nociceptor afferent fibers provide additional evidence for presynaptic localization of microORs on central C-, but not Adelta-terminals.
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Sex-related differences in the experience of clinical and experimental pain have been widely reported. Females are at elevated risk for developing several chronic pain conditions and women demonstrate greater sensitivity to noxious stimulation in the laboratory. However, relationships between responses to experimental noxious stimuli and the experience of clinical pain have not been well characterized. ⋯ Women with higher pain tolerances showed greater improvement in pain, more reduction in pain-related interference, and more increases in activity level than women with lower pain tolerances. In contrast, pain tolerance was not associated with positive treatment outcomes among men. These results indicate that experimental pain responses may be most clinically relevant for women, and that sex differences may exist in the determinants of pain-treatment outcomes.
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A series of health surveys are conducted every sixth to seventh year in Denmark. In the most recent survey of 2000, a national random sample (>16 years) was drawn from the Danish Central Personal Register. Out of the original sample 12,333 (74%) were interviewed and of these 10,066 returned a completed questionnaire (SF-36). ⋯ Among the persons in the PG, 33% were not satisfied with the examinations carried out in connection with their pain condition and 40% were not satisfied with the treatment offered. Nearly 130,000 adults, corresponding to 3% of the Danish population, use opioids on a regular basis. Opioids are used by 12% of the PG.
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Comparative Study
Peripheral group II metabotropic glutamate receptors mediate endogenous anti-allodynia in inflammation.
We previously demonstrated that activation of peripheral group II mGluRs inhibits PGE2-induced thermal hyperalgesia. In the present study we examined the role of peripheral group II mGluRs in inflammation-induced mechanical allodynia in CD1 mice. Subcutaneous injection of group II mGluR agonists or antagonists into the plantar surface of the mouse hind paw did not alter mechanical thresholds, suggesting that peripheral group II mGluRs did not modulate basal mechanical sensation. ⋯ The application of group II mGluR antagonist (LY341495) alone delayed the recovery of PGE2- and carrageenan-induced mechanical allodynia. Three hours after injection of carrageenan, LY341495-injected mice showed little or no recovery with mechanical thresholds 8+/-1% of pre-carrageenan baselines, compared to 57+/-8% of pre-carrageenan baselines in vehicle-injected mice at the same time point. Our results suggest that activation of peripheral group II mGluRs reduces inflammation-induced mechanical allodynia and that peripheral group II mGluRs may mediate endogenous anti-allodynia effects, which speed recovery from inflammation-induced hypersensitivity.