Changes in the expression of Na_V1.7, Na_V1.8 and Na_V1.9 in a distinct population of dorsal root ganglia innervating the rat knee joint in a model of chronic inflammatory joint pain

Abstract

Voltage-gated sodium channels play an essential role in regulating the excitability of nociceptive primary afferent neurones. In particular the tetrodotoxin-sensitive (TTX-S) Na(V)1.7 and the tetrodotoxin-resistant (TTX-R) Na(V)1.8 and Na(V)1.9 channels have been suggested to play a role in inflammatory pain. Previous work has revealed acute administration of inflammatory mediators, such as Freund's complete adjuvant (FCA) or carrageenan caused an upregulation in the levels of Na(V)1.7 and Na(V)1.8 protein in DRG (dorsal root ganglia) tissue up to 4 days post-insult. In the present study, the expression of Na(V)1.7, Na(V)1.8 and Na(V)1.9 was examined over a 28 day timecourse during a rat model of FCA-induced chronic inflammatory joint pain. Using the retrograde tracer Fast Blue (FB) and specific Na(V)1.7, Na(V)1.8 and Na(V)1.9 sodium channel antibodies, immunohistochemical staining techniques were used to study sodium channel expression in a distinct population of L3-L5 knee joint afferent DRGs. In the ganglia, counts were made of positively labelled cells in the FB population. The results demonstrate that, following FCA injection, Na(V)1.9 expression is upregulated at days 14, 21 and 28 post-FCA, with Na(V)1.7 and Na(V)1.8 showing increased channel expression at days 14 and 28. These observations are accompanied by a unilateral joint hypersensitivity in the FCA-injected knee indicated by a behavioural shift in weight distribution measured using an incapacitance tester. The increased presence of these channels suggests that Na(V)1.7, Na(V)1.8 and Na(V)1.9 play a role, at least in part, in the maintenance of chronic inflammatory pain several weeks after the initial insult.

Evaluation of behavior and expression of NaV1.7 in dorsal root ganglia after sciatic nerve compression and application of nucleus pulposus in rats

“…Inflammation in rat hind paws was shown to induce NaV up-regulation in axons of digital nerves [32], and peripheral inflammation following carrageenan injection was reported to increase the expression of NaV1.7 in DRG neurons [33]. In addition, the expression of NaV1.7 in a distinct population of DRG innervating the rat knee joint was increased in a model of chronic inflammatory joint pain [34]. Furthermore, some authors have demonstrated a decrease in inflammatory hyperalgesia in response to herpes vector-mediated knockdown of NaV1.7 in primary afferents.…”

“…The current model includes elements of inflammation and compressive nerve injury, as mentioned above. Peripheral inflammation increases the expression of NaV1.7 in peripheral nerves and DRG [32][33][34]. Inflammation in rat hind paws was shown to induce NaV up-regulation in axons of digital nerves [32], and peripheral inflammation following carrageenan injection was reported to increase the expression of NaV1.7 in DRG neurons [33].…”

Topisches Ambroxol zur Behandlung neuropathischer Schmerzen

“…Auch die Attackenreduktion bei jedem unserer 5 betroffenen Patienten ist so eventuell erklärbar. Eine gesteigerte Na v 1.8-Expression findet sich ferner bei diabetischer Polyneuropathie [30], Smallfiber-Neuropathie [19], Radikulopathien [17,44], Trigeminusneuralgie [41], aber auch bei Arthrosen [39,43] und Knochenmetastasen [33]. Die Na v 1.8-Blockade, z.…”

Colonic Hypersensitivity and Sensitization of Voltage-gated Sodium Channels in Primary Sensory Neurons in Rats with Diabetes

“…Two isoforms of the α-subunit of VGSCs, Na V 1.7, and Na V 1.8, are expressed at high levels in nociceptive sensory neurons. 8 Multiple lines of evidence show that they have been implicated in the development of inflammatory pain 9,10 and neuropathic pain. [11][12][13] Furthermore, dysregulation of VGSCs in injured sensory neurons is also involved in the development of painful peripheral neuropathy in a rat model of diabetes.…”