Cold-allodynia

Compounds with moderate p-affinities are very potent in a variety of pain models in mice and rats. In addition to antinociceptive efficacy in models of acute pain (tail flick, writhing) these compounds inhibit acute and persistent inflammatory pain (Randall Selitto, formalin test). Furthermore, they show strong inhibition of acute visceral pain (colorectal distension) and of tactile and cold allodynia in models of neuropathic pain (spinal nerve ligation (Chung), chronic constriction injury (Bennett)). The data suggest these compounds to be potential candidates for the management of clinical pain indications. Somatic and visceral pain with and without inflammatory conditions as well as neuropathic pain might be addressed with this approach. 

Nerve injury, followed by pain related behaviour, is induced by loose ligation of the ischiatic nerve of one hind paw of the rat. 3-4 weeks after ligation, neuropathic pain-like behaviour is seen as increased sensitivity towards heat and pressure stimuli (hyperalgesia). Also pain reactions toward non-noxious tactile (mechanical allodynia) or cold stimuli (cold allodynia) can be observed. Mechanical allodynia is tested with von Frey hairs and cold allodynia by putting the animals on metal plate cooled to 4 °C. The number of paw liftings is counted (Bennett and Xie, Pain 1988, 33, 87-107). 

Some other related studies established that resveratrol can attenuate diabetic nephropathy in rats [Sharma et al., 2006a] and reduce thermal hyperalgesia and cold allodynia in streptozotozin-induced diabetic rats [Sharma et al., 2006b]. 

Sharma S, Kulkarni SK, Chopra K. 2006b. Resveratrol, a polyphenolic phytoalexin attenuates thermal hyperalgesia and cold allodynia in STZ-induced diabetic rats. Indian J Exp Biol 44 566-569. 

Ziconotide is neuroprotective in rat models of ischemic neuronal damage and after intrathecal administration, antinociception is observed in rats with limited toxicity. The neuroprotective effects observed in rat models are thought to be due to a reduction in body temperature. Analgesic effects are observed in cancer and AIDS patients whose pain was not relieved after opioid administration and in neuropathic conditions. Intrathecal administration of ziconotide prevents mechanical and cold allodynia and heat hyperalgesia " in neuropathic rats. The use of N-type VSCC inhibitors in both ischemic brain injury and pain treatment is complicated by their important role in the synapse. Adverse effects are observed in patients but they are managed through dose reduction or symptomatic treatment, although serious supraspinal and systemic adverse effects have been seen. ... 

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