Pain
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Comparative Study
Sex differences in temporal summation of pain and aftersensations following repetitive noxious mechanical stimulation.
Several studies demonstrate that women are more sensitive to experimental pain than men. In addition, women exhibit greater temporal summation of heat and mechanically evoked pain. Since temporal summation of pain is centrally mediated, its greater expression in women suggests a central nociceptive hyperexcitability relative to men. ⋯ Temporal summation of pain intensity and unpleasantness ratings were more pronounced in women than men (P<0.0001). In addition, significant temporal summation occurred only with 2 s interstimulus interval for men (P<0.0005) but with 2 and 5 s interstimulus interval for women (P<0.0001). Moreover, women provided greater ratings for the intensity and the unpleasantness of aftersensations (P<0.0005) and reported painful aftersensations at greater frequency (P<0.05) Greater temporal summation of pain and aftersensations in women suggests that their central processing of nociceptive input may be more easily upregulated into pathological hyperexcitability, possibly accounting for the higher prevalence of various chronic pain conditions among women.
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Comparative Study
Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients.
Taxol produces neuropathic pain with three distinct zones of involvement in the extremities. Most distally is an area of on-going pain and proximal to this is a zone of sensory disturbance but not overt pain. These two areas were confined in all but one case to the glabrous skin of the hands and/or feet. ⋯ In contrast to mechanical sensibility, thermal thresholds for warm and heat pain detection were normal throughout. Finally, chemotherapy patients showed paradoxical burning pain to skin cooling that was most pronounced in proximal areas of skin thought to be unaffected by the patients, intermediate in the border zone of altered sensibility and least pronounced in areas of on-going pain. These data suggest that taxol produces a neuropathy characterized by pronounced impairment of function in A-beta myelinated fibers, intermediate impairment of A-delta myelinated fibers, and a relative sparing of C-fibers.
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Comparative Study
Activation of extracellular signal-regulated protein kinase in dorsal horn neurons in the rat neuropathic intermittent claudication model.
Extracellular signal-regulated protein kinase (ERK) is a mitogen-activated protein kinase (MAPK) that mediates several cellular responses to mitogenic and differentiation signals, and activation of ERK in dorsal horn neurons by noxious stimulation is known to contribute to pain hypersensitivity. In order to elucidate the pathophysiological mechanisms of the cauda equina syndrome, secondary to spinal canal stenosis, we evaluated walking dysfunction triggered by forced exercise and activation of ERK in the dorsal horn using a rat model of neuropathic intermittent claudication. Rats in the lumbar canal stenosis (LCS) group showed a shorter running distance from 1 to 14 days after surgery. ⋯ In addition, a prostaglandin E1 analog, OP-1206 alpha-CD, administered orally, improved the walking dysfunction, and further, inhibited activation of ERK following running 7 days after surgery. These findings suggest that intermittent claudication triggered by forced walking might affect the phosphorylation of ERK in the superficial laminae, possibly via transient (partial) ischemia of the spinal cord. ERK activation in the dorsal horn neurons may be involved in the transient pain in the neuropathic intermittent claudication model.
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Comparative Study
Ethosuximide reverses paclitaxel- and vincristine-induced painful peripheral neuropathy.
Paclitaxel (Taxol) is one of the most effective and frequently used chemotherapeutics for the treatment of solid tumours. However, paclitaxel produces peripheral neurotoxicity with patients reporting sensory abnormalities and neuropathic pain during and often persisting after paclitaxel therapy. The mechanisms underlying this dose-limiting side effect are currently unknown and there are no validated drugs for its prevention or control. ⋯ Repetitive dosing with ethosuximide (i.p. 100 or 300 mg/kg daily for 3 days) showed a dose-related consistent reversal of mechanical allodynia/hyperalgesia with no evidence of tolerance. Ethosuximide (i.p. 300 mg/kg) also reversed paclitaxel-induced cold allodynia and vincristine-induced mechanical allodynia/hyperalgesia. These data suggest that T-type calcium channels may play a role in chemotherapy-induced neuropathy and moreover identify ethosuximide as a new potential treatment for chemotherapy-induced pain.