European journal of pain : EJP
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Studies of sensory function following cortical lesions have often included lesions which multiple cortical, white matter, and thalamic structures. We now test the hypothesis that lesions anatomically constrained to particular insular and parietal structures and their subjacent white matter are associated with different patterns of sensory loss. Sensory loss was measured by quantitative sensory testing (QST), and evaluated statistically within patients relative to normal values. ⋯ These results suggest that nonpainful cold and heat sensations are jointly mediated by parietal and insular cortical structures so that lesions anywhere in this system may diminish sensitivity. In contrast, thermal pain is more robust requiring larger cortical lesions of these same structures to produce hypoalgesia. In addition, cold allodynia can result from restricted lesions that also produce thermal hypoesthesia, but not from all such lesions.
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Agonists of the TRPV1 receptor excite TRPV1-expressing polymodal nociceptors that is followed after higher doses by a state of diminished responsiveness called desensitization which ensues at two levels: (i) diminished responsiveness of the ion channel (TRPV1 receptor desensitization); (ii) diminished responsiveness of the nerve endings to all stimuli including noxious heat. The aim was to compare these desensitizing actions of TRPV1 agonists in the rat by measuring with an incremental hot/cold plate the noxious heat and cold thresholds, i.e. the lowest hot and highest cold plate temperature, respectively, that evokes nocifensive behaviour. Capsaicin (3.3-1000 nmol) or resiniferatoxin (0.016-0.5 nmol) applied intraplantarly evoked a sustained dose-dependent elevation of the noxious heat threshold lasting for 2-11 days. ⋯ The diminished acute nocifensive and heat threshold-lowering effects of resiniferatoxin or N-oleoyldopamine by pretreatment with doses that failed to elevate the heat threshold and to alter the nocifensive action of the TRPA1 activator formaldehyde, were taken as indication of TRPV1 receptor desensitization. In conclusion, using measurement of threshold temperatures eliciting nocifensive reactions in rats both in the hot and cold range revealed that capsaicin and RTX impair thermosensation in both noxious ranges due to a functional desensitization of peripheral terminals of TRPV1-expressing sensory neurons responsible for noxious heat and cold responsiveness. This could be differentiated from desensitization of TRPV1 receptor evoked by lower doses of resiniferatoxin or N-oleoyldopamine.
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Although many types of nerve damage can cause neuropathic pain, there are substantial commonalities in neuropathic pain symptoms, and patients can be divided into sub-groups based on their symptom profile rather than etiology. Mechanism-based treatment suggests that pharmacotherapy should be chosen be based shared commonalities of symptoms rather than etiology. The aim of the present study was to determine whether type of injury (etiology) or behavioral endpoint (symptom) is a better predictor of pharmacological responsivity in the most commonly used rodent models of neuropathic pain. ⋯ Hypersensitivity to heat and pressure were highly responsive to oxycodone, gabapentin, and amitriptyline; whereas cold and mechanical allodynia were more difficult to reverse. Moreover, CCI- and SNL-induced mechanical allodynia was completely insensitive to amitriptyline treatment. We conclude that regardless of model and time course of presentation, different symptoms of peripheral neuropathy have unique pharmacological responses.