Chronic Allodynia Research Articles

Effects of intrathecal vs. systemic clonidine in treating chronic allodynia-like response in spinally injured rats

A chronic pain-like response to innocuous mechanical stimuli (allodynia) was observed in rats after severe spinal cord ischemia, which resembled some painful conditions observed in spinally injured patients. The present studies examined the effects of clonidine, an α 2-adrenoceptor agonist, on this allodynia-like response. Intrathecal (i.t.) clonidine dose-dependently relieved allodynia and doses up to 10 μg did not induce motor deficits or sedation, but slightly increased systemic blood pressure. The anti-allodynic effect of i.t. clonidine was reversed by the selective α 2-adrenoceptor antagonist atipamezole. In contrast, 50 and 100 μg/kg intraperitoneal (i.p.) clonidine did not relieve the chronic allodynia, although the higher dose induced some motor deficits and sedation. Allodynic behavior was abolished after 200 μg/kg, i.p. clonidine, which, however, caused strong sedative and motor impairment. The present data suggested that spinal, but not systemic, α 2-adrenoceptor agonists may have therapeutic value in treating mechanical allodynia in patients with neuropathic pain of spinal origin.

Treatment of a chronic allodynia-like response in spinally injured rats: effects of systemically administered nitric oxide synthase inhibitors

We have previously reported that we have observed chronic pain-like response to light mechanical stimuli (allodynia) in rats after severe spinal cord ischemia, which resembles some painful conditions in chronic spinally injured patients and is not relieved by a number of conventional analgesics used for treating chronic neuropathic pain. In the present study, we tested the effects of the non-selective nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and the selective neuronal NOS inhibitor 7-nitro indazole (7-NI) and 6-nitro indazole (6-NI) on the chronic allodynia-like behavior. Systemic L-NAME dose-dependently relieved mechanical allodynia-like response in a stereo-specific and l-arginine-reversible manner without causing sedation or motor deficits. However, L-NAME significantly elevated systemic blood pressure. Systemic 7-NI relieved chronic allodynia in a l-arginine reversible manner, did not increase blood pressure or induce sedation, but caused motor deficits at a high dose, which was not reversed by l-arginine. Systemic 6-NI also relieved the chronic allodynia, which was however associated with severe sedation. In order to exclude the possibility that the effect of L-NAME on blood pressure was involved in the analgesic effect observed, the effect of systemically applied adrenaline was examined. Adrenaline increased the systemic blood pressure to a similar extent as L-NAME, but did not relieve allodynia. It is suggested that blockade of NOS by L-NAME relieved the chronic allodynia-like behavior in spinally injured rats. This effect was likely to be mediated by a blockade of neuronal isoforms of NOS, as 7-NI relieved the allodynia in a l-arginine-reversible manner. Consequently, generation of NO by neuronal NOS may be critically involved in the maintenance of this abnormal pain-related sensation. The possibility of using NOS inhibitors as potential novel analgesics is discussed.

Ephaptic coupling of large fibers as a clue to mechanism in chronic neuropathic allodynia following damage to dorsal roots

Ephaptic coupling of large fibers as a clue to mechanism in chronic neuropathic allodynia following damage to dorsal roots