Articles: hyperalgesia.
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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.
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Comparative Study
Sympathetic facilitation of hyperalgesia evoked from myofascial tender and trigger points in patients with unilateral shoulder pain.
To provide evidence for the sympathetic-sensory interaction within a trigger point, which may contribute to local and referred pain and sympathetic symptoms in myofascial pain syndrome. ⋯ Sympathetic hyperactivity needs to be considered during the clinical evaluation and management of myofascial pain syndrome.
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The present study investigated whether the loss of spinal mu-opioid receptors following peripheral nerve injury is related to mechanical allodynia. We compared the quantity of spinal mu-opioid receptor and the effect of its antagonists, such as naloxone and CTOP, on pain behaviors in two groups of rats that showed extremely different severity of mechanical allodynia 2 weeks following partial injury of tail-innervating nerves. One group (allodynic group) exhibited robust signs of mechanical allodynia after the nerve injury, whereas the other group (non-allodynic group) showed little allodynia despite having suffered the same nerve injury. ⋯ Intraperitoneal naloxone (2 mg/kg, i.p.) and intrathecal CTOP (10 microg/rat, i.t.) administration dramatically induced mechanical allodynia in the non-allodynic group. However, as in naïve animals, neither the loss of spinal mu-opioid receptors nor antagonist-induced mechanical allodynia was observed in the rats that had recovered from mechanical allodynia. These results suggest that the loss of spinal mu-opioid receptors following peripheral nerve injury is related to mechanical allodynia.