The Effect of Intradermal Norepinephrine on Allodynia in a Neuropathic Pain Rat Model

Abstract

Background: A spinal nerve ligation (SNL) injury may produce a neuropathic pain syndrome that includes tactile allodynia. This pain state may be diminished by sympathectomy. Intradermal (I.D.) injection of norepinephrine (NE) evokes pain in patients with sympathetically maintained pain. Recently, we reported the effect of intrathecal (I.T.) brimonidine and rilmenidine on the sympathetic nervous system. Therefore, we conducted a behavioral test to investigate the effects of sympathetic stimulation by I.D. NE on mechanical allodynia in rats with a SNL injury. Methods: Male SD rats were prepared with ligation of the left lumbar 5th and 6th spinal nerves and lumbar I.T. catheter implantation. NE 10g I.D. was administered in normal and SNL rats to investigate the change of cutaneous sensitivity to tactile stimuli. NE 30g I.D. was administered before and after I.T. injection of brimonidine 3g and rilmenidine 30g in SNL rats. Using a von Frey hair (VFH) test, we examined the effects of NE on the withdrawal threshold. Allodynic thresholds for the withdrawal response of the lesioned hindpaw to VFH stimuli were assessed. Results: Intradermal NE produced a reduction of the withdrawal threshold in normal and allodynic rats. An allodynic state induced by a SNL was aggravated by NE. In allodynic rats, the baseline threshold of a lesioned left hindpaw was markedly low and such a state was maintained during the behavioral experiment. The antiallodynic effects of I.T. brimonidine and rilmenidine were produced in both pre- and post-treatment of NE. Conclusions: The results suggest that a sympathetic component is likely involved in the mechanism of mechanical allodynia produced by a SNL injury.