Gabapentin for spasticity and autonomic dysreflexia after severe spinal cord injury

Abstract

Study DesignUtilizing a complete transection spinal cord injury (SCI) model at the fourth thoracic vertebral level in adult rats, we evaluated whether blocking noxious stimuli below the injury diminishes abnormal somatic and autonomic motor reflexes, manifested in muscular spasticity and hypertensive autonomic dysreflexia, respectively. Gabapentin (GBP) is well-tolerated and currently used to manage neuropathic pain in the SCI population; evidence suggests it acts to decrease presynaptic glutamate release. Since clinical evidence indicates that GBP may suppress muscular spasticity in the chronic SCI population, we hypothesized that preventing neurotransmission of noxious stimuli with GBP eliminates a critical physiological link to these distinct, debilitating SCI-induced secondary impairments.ObjectivesBehavioural assessments of tail muscle spasticity and mean arterial blood pressure responses to noxious somatic and/or visceral stimulation were used to test the effects of GBP on these abnormal reflexes.SettingLexington, KentuckyMethodsWe employed femoral artery catheterization and radio-telemetric approaches to monitor blood pressure alterations in response to noxious colorectal distension (CRD) weeks after complete SCI.ResultsAt 2-3 weeks post-SCI, acute GBP administration (50 mg/kg, i.p.) significantly attenuated both autonomic dysreflexia and tail spasticity induced by noxious stimuli compared to saline-treated cohorts.ConclusionThese results demonstrate, for the first time, that a single pharmacological intervention, GBP, can effectively attenuate the manifestation of both muscular spasticity and autonomic dysreflexia in response to noxious stimuli.

Autonomic Consequences of Spinal Cord Injury

“…Pharmacological approaches are currently applied to patients with SCI to treat autonomic problems in the clinical arena, while traditional palliative methods may soon be replaced with preventative methods (280,281). Although numerous attempts have been implemented to induce injured CNS axon regeneration for sensory and motor functional recovery, the aim of finding a cure for paralysis has not yet been achieved.…”

“…Antisympathetic drugs consist of ganglionic blockers and catecholaminergic antagonists, which often have immediate effects for responsive hypertension (122). A presynaptic calcium channel blocker, gabapentin (113,361), widely used for the treatment of neuropathic pain and epilepsy, is reported to alleviate both experimental spasticity and autonomic dysreflexia by eliminating a physiological link between these aberrant reflexes, impeding neurotransmission of noxious stimuli into the spinal cord (281,282).…”

Latest Approaches for the Treatment of Spasticity and Autonomic Dysreflexia in Chronic Spinal Cord Injury

“…Although numerous individuals with SCI are using gabapentin for the management of neuropathic pain, to date there has been no clinical evaluation of its potential efficacy in managing the incidence or severity of autonomic dysreflexia. On the contrary, however, it has recently been reported that gabapentin has striking efficacy in reducing both the severity of CRD-evoked dysreflexic hypertension and tail spasticity in response to stretch or painful pinch, in the same injured animals, weeks following complete SCI [97,98].…”

Possible Sites of Therapeutic Action in Restless Legs Syndrome: Focus on Dopamine and α₂δ Ligands

“…It is important to note that the hypotha- [112,113,115,117,123,125]. ␣ 2 ␦ subunits: [116,142,144,145,147,[150][151][152]. GBP = Gabapentin; IML = intermediolateral nucleus; PGB = pregabalin.…”

“…␣ 2 ␦ -containing calcium channels are found at various locations within the proposed RLS circuit ( fig. 2 ), including the dorsal horn [144] , dorsal root ganglia neurons [139,142,[144][145][146][147][148][149] , intermediolateral neurons [150] , and sympathetic pre-and postganglionic neurons [151,152] . Thus, they are in a prime position to control the excitability of the circuitry at the various points that may be involved in the symptomatology of RLS.…”