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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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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While spontaneous and stimulus-evoked pain are the hallmarks of complex regional pain syndrome (CRPS), also known as reflex sympathetic dystrophy, autonomic abnormalities, motor dysfunction, and trophic changes in the affected limb are additional clinical characteristics distinguishing this syndrome. Even though the exact underlying mechanisms of the syndrome remain obscure, a recent hypothesis suggests that the abnormal response of neural nociceptive tissue plays a major role in the pathogenesis of CRPS via the mechanism known as 'neurogenic inflammation'. The group of patients presented here exhibited all the clinical characteristics of CRPS but had no pain, thereby indicating that ongoing or evoked pain is not a necessary condition for CRPS to be maintained. We suggest the term complex regional painless syndrome to describe this syndrome.
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Comparative Study
Individual differences in diffuse noxious inhibitory controls (DNIC): association with clinical variables.
Laboratory pain research has been criticized as being irrelevant to the clinical experience of pain. Previous findings have been inconsistent with some studies suggesting that experimental pain responses may be related to the reported presence or severity of chronic pain, while others report no such associations. However, few of these studies assess a variety of laboratory pain responses, and none has assessed relationships between clinical pain and diffuse noxious inhibitory controls (DNIC) in healthy subjects. ⋯ Of the laboratory pain variables, only DNIC was the sole consistent predictor of clinical pain and physical health, with greater DNIC responses related to less pain, better physical functioning, and better self-rated health. In addition, age differences in DNIC appeared to partially mediate age differences in physical functioning. These findings highlight the potential clinical relevance of experimental pain procedures and suggest that DNIC may be the laboratory pain response most closely associated with clinical pain and health-related variables.