Effects of purinergic and adrenergic antagonists in a rat model of painful peripheral neuropathy.

In previous studies, pain behaviors produced in the spinal nerve ligation rat model of neuropathic pain were partly reduced by surgical lumbar sympathectomy. However, systemic injection of phentolamine, an alpha-adrenoceptor blocker, was not effective in reducing pain behaviors, at least in the Sprague-Dawley strain of rats. This suggests that sympathectomy removes not only adrenoceptor function but also other factors that must contribute importantly to the generation of neuropathic pain behaviors. Since the purinergic substance adenosine 5'-triphosphate (ATP) is known to be co-released with norepinephrine (NE) from the sympathetic nerve terminals, we hypothesized that ATP might be involved in the sympathetic dependency of neuropathic pain. The present study tested this hypothesis by examining the effects of systemic injection of an adrenoceptor blocker (phentolamine), a purinoceptor blocker (suramin), and a combination of these two on behavioral signs of mechanical allodynia in the spinal nerve ligation model of neuropathic pain. The results of the present study showed two novel findings. First, the mechanical hypersensitivity (allodynia) resulting from the L5/6 spinal nerve ligation can be reduced either by sympathetic block accomplished by application of a local anesthetic or by surgical sympathectomy of the L2-L6 sympathetic ganglia. Second, suramin (at 100 mg/kg, i.p.) can reduce mechanical hypersensitivity in neuropathic rats when given in combination with 5 mg/kg of phentolamine. This effect was observed in a subset of neuropathic rats, and the drug responses were consistent in repeated treatments within the animal group. Neither phentolamine nor suramin changed the mechanical sensitivity of neuropathic rats when given alone. The data suggest that the purinergic substance ATP is co-released with NE from sympathetic nerve terminals and these two are together involved, at least in part, in the maintenance of the sympathetically dependent component of pain behaviors in some neuropathic rats.