Distinct Membrane Effects of Spinal Nerve Ligation on Injured and Adjacent Dorsal Root Ganglion Neurons in Rats

Abstract

These findings indicate that nerve injury-induced electrical instability is restricted to axotomized neurons and is absent in adjacent intact neurons.

Opposing effects of spinal nerve ligation on calcium-activated potassium currents in axotomized and adjacent mammalian primary afferent neurons

“…Several studies have indicated that medium sized somata with axons of Aδ-fiber caliber exhibit significant phenotypic changes after nerve injury, and may be an important generator of ectopic discharges [11,23,53,55,56,63,98]. In addition, a previous study from our lab showed that Aδ fibers exhibited the most pronounced electrophysiological changes after SNL, and in particular increased AP duration, decreased AHP amplitude and duration, and increased repetitive firing during sustained depolarization, manifestations that may explain increased neuronal excitability and hyperalgesia in neuropathic pain states [80].…”

“…The presence and role of I K(Ca) channels in neurons is unclear [78]. Altered regulation of AP kinetics and repetitive firing is particularly important in the pathogenesis of increased excitability of peripheral sensory neurons after nerve injury [80]. Nevertheless, the presence of different categories of K (Ca) channels in primary afferent neurons, as well as the influence of injury on these channels, is incompletely investigated [4].…”

Oxycodone Plus Ultra-Low-Dose Naltrexone Attenuates Neuropathic Pain and Associated μ-Opioid Receptor–Gs Coupling

“…[1][2][3][4]10,34,52,66,80 Upregulation of cytokine receptor mRNA in the sciatic nerve and dorsal root ganglion after partial spinal nerve ligation has been noted, and SNL has also been reported to decrease MOR density in injured peripheral axons in the ipsilateral Lamina I of dorsal horn, leading to changes in presynaptic-and postsynapticevoked responses of MOR-containing fiber. 2,46,59 These synaptic changes include a decrease in presynaptic MOR-mediated inhibition, reduced inhibition of the miniature EPSP in substantia gelatinosa neurons, a shortened afterhy-perpolarization duration in C-fibers in the L 5 dorsal root ganglion, and increased repetitive firing of Aδ-fibers during sustained depolarization. 46,59 In this study, we demonstrate a nerve injury-induced neuroplastic alteration in MOR-G protein coupling profile in ipsilateral lumbar spinal cord tissue of SNL animals.…”

“…2,46,59 These synaptic changes include a decrease in presynaptic MOR-mediated inhibition, reduced inhibition of the miniature EPSP in substantia gelatinosa neurons, a shortened afterhy-perpolarization duration in C-fibers in the L 5 dorsal root ganglion, and increased repetitive firing of Aδ-fibers during sustained depolarization. 46,59 In this study, we demonstrate a nerve injury-induced neuroplastic alteration in MOR-G protein coupling profile in ipsilateral lumbar spinal cord tissue of SNL animals.…”

“…2,46,59 These synaptic changes include a decrease in presynaptic MOR-mediated inhibition, reduced inhibition of the miniature EPSP in substantia gelatinosa neurons, a shortened afterhy-perpolarization duration in C-fibers in the L 5 dorsal root ganglion, and increased repetitive firing of Aδ-fibers during sustained depolarization. 46,59 In this study, we demonstrate a nerve injury-induced neuroplastic alteration in MOR-G protein coupling profile in ipsilateral lumbar spinal cord tissue of SNL animals.Although we previously showed that chronic opioid administration causes a shift in MOR-G protein coupling from G i/o to G s , 74 we now show that SNL injury induces this novel MOR-G s coupling ipsilateral to the injury without changing the extent of coupling to G i/o proteins. Chronic oxycodone administration to nerve-injured rats contributed to this G s coupling, as chronic oxycodone treatment significantly enhanced the level of G s coupling compared with that seen in the ipsilateral dorsal horn of vehicle-treated SNL animals.…”