Sodium channel β1 and β2 subunits parallel SNS/PN3 α-subunit changes in injured human sensory neurons

Abstract

Voltage-gated sodium channels consist of a pore-containing alpha-subunit and one or more auxiliary beta-subunits, which may modulate channel function. We previously demonstrated that sodium channel SNS/PN3 alpha-subunits were decreased in human sensory cell bodies after spinal root avulsion injury, and accumulated at injured nerve terminals in pain states. Using specific antibodies for immunohistochemistry, we have now detected sodium channel beta1 and beta2 subunits in sensory cell bodies within control human postmortem sensory ganglia (78% of small/medium (< or = 50 microm) and 68% of large (> or = 50 microm) cells); their changes in cervical sensory ganglia after avulsion injury paralleled those described for SNS/PN3 alpha-subunits. Our results suggest that alpha- and beta-subunits share common regulatory mechanisms, but present distinct targets for novel analgesics.

Differential Expression of Sodium Channel β Subunits in Dorsal Root Ganglion Sensory Neurons

“…These studies indicate that all four isoforms of ␤ subunits (␤ 1 -␤ 4 ) are present in the DRG and that these subunits are differentially expressed in subpopulations of sensory neurons (12,15). ␤ 3 subunits are prominently expressed in small and medium neurons, whereas ␤ 1 and ␤ 4 are preferentially expressed in large neurons (4,16,17).…”

“…Much of what is currently known about ␤ subunit expression in the DRG has been derived from immunocytochemistry and in situ hybridization (4,12,(15)(16)(17)(18)44). These studies indicate that all four isoforms of ␤ subunits (␤ 1 -␤ 4 ) are present in the DRG and that these subunits are differentially expressed in subpopulations of sensory neurons (12,15).…”

“…␤ subunits are relatively small proteins (33-36 kDa) composed of a single membrane-spanning ␣ helix, a short intracellular C terminus, and a large extracellular N terminus incorporating an immunoglobulin-like fold similar to that found in adhesion molecules (8,13). Immunocytochemistry and in situ hybridization indicate that all four isoforms of the ␤ subunit (␤ 1 -␤ 4 ) are expressed in sensory neurons (12,14,15).…”

Effects of PKC and PKA Inhibitors on the cAMP-Stimulant-Induced Enhancement of Tetrodotoxin-Resistant Na+ (Nav1.8) Currents

“…These observations lead us to suggest the Nav1.8 channel plays a potential role in the sensation of neuropathic pain [16]. Indeed, it has been demonstrated that human patients with chronic neurogenic pain or chronic local hyperalgesia show increased Nav1.8 channel expression proximal to a peripheral injury site [17][18][19]. Nav1.8 channels are cloned from rat DRG neurons and the expression of these channels is sensitive to capsaicin [20].…”

A Review of Intravenous Lidocaine Infusion Therapy for Paediatric Acute and Chronic Pain Management

“…A number of different sodium channel isoforms exist with distinct tissue distribution and possibly distinct physiological functions. Some of these isoforms have been shown to be up-regulated in inflammatory and neuropathic pain states [28,[154][155][156].…”