Articles: hyperalgesia.
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The aim of this study was to investigate involvement of central mechanisms in complex regional pain syndrome (CRPS). In particular, we wished to determine whether hyperalgesia extends ipsilaterally from the affected limb to the forehead. The heat-pain threshold, pressure-pain threshold, and ratings of cold and sharpness were investigated on each side of the forehead and in the affected and unaffected limbs of 38 patients with features of CRPS. ⋯ Although the heat-pain threshold and ratings of sharpness and cold did not differ between the two sides of the forehead in the group as a whole, the sharpness of pinprick sensations in the affected limb was mirrored by similar sensations in the ipsilateral forehead. Conversely, diminished sensitivity to light touch in the affected limb was associated with diminished sensitivity to sharpness, cold and heat-pain in the ipsilateral forehead. These findings suggest that central nociceptive processing is disrupted in CRPS, possibly due to disturbances in the thalamus or higher cortical centres.
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Experimental neurology · Jul 2006
Comparative StudyAntisense knock down of TRPA1, but not TRPM8, alleviates cold hyperalgesia after spinal nerve ligation in rats.
Patients with neuropathic pain frequently experience hypersensitivity to cold stimulation. However, the underlying mechanisms of this enhanced sensitivity to cold are not well understood. After partial nerve injury, the transient receptor potential ion channel TRPV1 increases in the intact small dorsal root ganglion (DRG) neurons in several neuropathic pain models. ⋯ In the injured L5 DRG, on the other hand, both TRPA1 and TRPM8 expression decreased over 2 weeks after ligation. Furthermore, intrathecal administration of TRPA1, but not TRPM8, antisense oligodeoxynucleotide suppressed the L5 SNL-induced cold hyperalgesia. Our data suggest that increased TRPA1 in uninjured primary afferent neurons may contribute to the exaggerated response to cold observed in the neuropathic pain model.
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Antidepressants such as tricyclic antidepressants have become used to treat a variety of chronic pain conditions. However, the side effects are dose-limiting in the treatment of chronic pain. Milnacipran is a norepinephrine/serotonin reuptake inhibitor that does not have the severe side effects associated with traditional tricyclic antidepressants. The effects of intrathecal and systemic administration of milnacipran on spinal nerve ligation (SNL)-induced thermal and mechanical hypersensitivity and shift in weight bearing were determined. Intrathecal administration of milnacipran was found to reverse both SNL-induced thermal and tactile (to von Frey filaments) hypersensitivity, as well as shift in weight bearing. Acute systemic administration of milnacipran also reversed nerve injury-induced thermal hypersensitivity for up to 5 hours but failed to reverse tactile hypersensitivity or shift in weight bearing. Of note, both intrathecal and subcutaneous administration of milnacipran induced thermal antinociception in both SNL and sham rats. Chronic (daily) systemic administration of milnacipran alleviated both thermal hypersensitivity and shift in weight bearing, with both acute and chronic effects observed on thermal hypersensitivity. However, chronic systemic milnacipran administration failed to alleviate tactile hypersensitivity to von Frey filaments. These results indicate that different mechanisms underlie shift in weight bearing, thermal hypersensitivity, and tactile hypersensitivity. ⋯ These results indicate that the ability of milnacipran to relieve nerve injury-induced allodynia, hyperalgesia, and shift in weight bearing depends on the route of administration and the duration of treatment, with alleviation of SNL-induced tactile hypersensitivity and shift in weight bearing as a result of activity within the central-rather than the peripheral-nervous system.
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The susceptibility of changes in responsiveness to noxious cold stimulation of rats submitted to chronic constriction of the infraorbital nerve (CION) or carrageenan to drug inhibition was compared. Nocifensive responses were measured as total time rats engaged in bilateral facial grooming with both forepaws over the first 2 min following tetrafluoroethane spray application to the snout. Carrageenan (50 microg, s.c. into upper lip) caused short-lived ipsilateral cold hyperalgesia (peak at 3 h: vehicle 8.4+/-1.3, carrageenan 21.2+/-3.0 s) which was markedly suppressed by i.p. indomethacin (4 mg/kg), celecoxib (10mg/kg) or s.c. dexamethasone (0.5 mg/kg), endothelin ET(A) or ET(B) receptor antagonists (BQ-123 and BQ-788, respectively; 10 nmol/lip). ⋯ Bosentan (dual ET(A)/ET(B) receptor antagonist, 10 mg/kg, i.v.) abolished CION-induced cold hyperalgesia for up to 6h. Thus, once established, CION-induced orofacial hyperalgesia to cold stimuli appears to lack an inflammatory component, but is alleviated by endothelin ET(A) and/or ET(B) receptor antagonists. If this CION injury model bears predictive value to trigeminal neuralgia (i.e., paroxysmal orofacial pain triggered by various stimuli), endothelin receptors might constitute new targets for treatment of this disorder.
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Comparative Study
Involvement of the TTX-resistant sodium channel Nav 1.8 in inflammatory and neuropathic, but not post-operative, pain states.
Antisense (AS) oligodeoxynucleotides (ODNs) targeting the Nav 1.8 sodium channel have been reported to decrease inflammatory hyperalgesia and L5/L6 spinal nerve ligation-induced mechanical allodynia in rats. The present studies were conducted to further characterize Nav 1.8 AS antinociceptive profile in rats to better understand the role of Nav 1.8 in different pain states. Consistent with earlier reports, chronic intrathecal Nav 1.8 AS, but not mismatch (MM), ODN decreased TTX-resistant sodium current density (by 60.5+/-10.2% relative to MM; p<0.05) in neurons from L4 to L5 dorsal root ganglia and significantly attenuated mechanical allodynia following intraplantar complete Freund's adjuvant. ⋯ Finally, Nav 1.8 AS, but not MM, ODN treatment produced a small but significant attenuation of acute noxious mechanical sensitivity in naïve animals (17.6+/-6.2% effect, p<0.05 vs. MM). These data demonstrate a greater involvement of Nav 1.8 in frank nerve injury and inflammatory pain as compared to acute, post-operative or chemotherapy-induced neuropathic pain states.