Pain
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Patients with fibromyalgia syndrome (FMS) report chronic pain related to abnormal sensitivity of muscles that is reflected by so-called tender points (TP). TP represent areas of abnormal mechanical pain thresholds that have only shown a minor correlation with clinical pain of FMS patients and seem to be better suited for predicting distress. Pain-related negative affect (PRNA), abnormal temporal summation of second pain (termed wind-up or WU), and abnormal WU decay are frequently present in FMS patients. ⋯ Hierarchical regression analysis demonstrated that the combination of PRNA ratings, TP count, and WU decay ratings predicted 49.7% of the variance of clinical pain in FMS. This model demonstrates independent relationships of biological and psychological factors to clinical pain and underscores the important role of abnormal peripheral and central pain mechanisms for FMS. Therefore, the combination of PRNA, TP count, and WU decay may provide an excellent measure for future clinical studies of FMS patients.
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Secondary mechanical hyperalgesia has been demonstrated in postoperative patients indicating that central sensitization occurs after surgery. However, the underlying mechanisms are unknown. Here, we studied the role of spinal N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate receptors for pain behaviors indicating secondary hyperalgesia caused by gastrocnemius incision in the rat. ⋯ These results indicate that spinal sensitization contributing to behaviors for secondary hyperalgesia after incision requires Ca(2+) permeable AMPA/kainate receptors. The data further demonstrate that behaviors for secondary mechanical hyperalgesia after incision can be inhibited without affecting behaviors for primary mechanical hyperalgesia and guarding. Mechanisms for central sensitization causing secondary hyperalgesia in postoperative patients may therefore be separated from spontaneous pain and hyperalgesia that arises adjacent to the area of the incision.
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The aim of the study was to investigate the perceptual integration of simultaneous stimulation in a focal and a referred pain area to investigate whether referred pain is mainly caused by facilitation of on-going input from the referred pain area by stimulation in the focal pain area or if referred pain is a consequence of misinterpretation of the origin of inputs from the focal pain area. Pain was induced in twelve healthy individuals by intramuscular electrical stimulation in the left infraspinatus muscle (MI) or the left dorsolateral upper arm (UA), i.e. the area of referral commonly reported from stimulation in MI. Conditioning stimulation consisted of, in a counterbalanced order, no stimulation (baseline) and pain intensity rated as 2/10 and 4/10, respectively, on a category scale. ⋯ In conclusion, an effect at pain threshold level only was documented during simultaneous stimulation in the focal and referred pain area, which does not support facilitation of inputs from the referred pain area as the main mechanism generating referred pain. Instead, referred pain is most likely a consequence of misinterpretation of the origin of input from the stimulated focal pain area, due to excitation of neurones somewhere along the neuroaxis with projected fields in the referred pain area. The fact that conditioning stimulation in m. infraspinatus generated referred pain in the dorsolateral upper arm, but not vice versa suggests that the divergence of the input is not reciprocally arranged.
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Comparative Study
Comparative activity of the anti-convulsants oxcarbazepine, carbamazepine, lamotrigine and gabapentin in a model of neuropathic pain in the rat and guinea-pig.
Anti-epileptic drugs (AEDs) are increasingly used for the treatment of neuropathic pain. Oxcarbazepine is a recently introduced AED that is effective in treating epilepsy and has an improved side-effect profile compared to existing therapies. Here we have examined the effect of oxcarbazepine and other AEDs in a model of neuropathic pain in the rat and guinea-pig. ⋯ Gabapentin was poorly active against mechanical hyperalgesia in both the rat and guinea-pig following a single oral administration (100 mg x kg(-1)), although upon repeated administration it produced up to 70 and 90% reversal in rat and guinea-pig, respectively. Gabapentin did however produce significant dose-related reversal of tactile allodynia in the rat following a single administration. These data show that oxcarbazepine and other AEDs are effective anti-hyperalgesic or anti-allodynic agents in an animal model of neuropathic pain, and provide further support for their use in the treatment of neuropathic pain in the clinic.
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In male rats, carrageenan (CAR)-induced inflammation or exposure to a selective protein kinase C epsilon (PKC epsilon ) agonist (psi epsilon RACK) produces prolongation of the hyperalgesia induced by a subsequent exposure to an inflammatory mediator, a phenomenon referred to as hyperalgesic priming. Since many chronic inflammatory conditions are sexually dimorphic, we tested the hypothesis that hyperalgesic priming is sexually dimorphic. Prior injection of CAR or psi epsilon RACK produced a prolongation of the hyperalgesia induced by a subsequent injection of prostaglandin E(2), from less than 3 h to greater than 24 h, but only in male rats. ⋯ While gonadectomy in males had no effect on CAR and psi epsilon RACK induced hyperalgesic priming, female phenotype was observed following implantation of estrogen in males. Thus, mechanisms mediating the development of hyperalgesic priming produced by inflammation are suppressed by estrogen. This regulation of priming by estrogen appears to occur at or downstream of the activation of PKC epsilon.