Sodium channel function in neuropathic pain
Sodium channels were discussed as new inroads for reducing neuropathic pain.
At the 6th International Congress on Neuropathic Pain (NeuPSIG 2017 at Gothenburg, Sweden) the latest research and development data were presented and discussed related to the mechanisms, assessment, prevention and treatment of neuropathic pain.
Three different types of neuropathic pain?
Professor Ralf Baron presented a preliminary talk on 3 different types based on sensory testing (QST testing for phenytypical differentiation), one based on sensory loss based on degeneration of small and large fibres (numbness), one on preserved thermal fibres and thermal hyperalgesia, and one with mechanical hyperalhesia (combination of loss in small fibres and a gain in dynamic hyperalgesia) and tried to link the patterns to different pathophysiological mechanisms. The idea is to differentiate patient populations using these 3 subgroups and analyse the differential response to various drugs (responders versus non-responders).
Oxcarbamezepin (a sodium channel blocker) for instance in a thermal hyperalgesia versus sensory loss group (prospective stratification), clearly the reduction of pain by oxcarbamazepin was much more robust in the thermal hyperalgesia group versus the sensory loss population.
Sodium channel functions in neuropathic pain
One of the new and interesting topics was the role of the sodium channel in neuropathic pain.
In the 4th workshop at the congres, on the 15th of June some important issues were discussed.
Workshop 4: Testing sodium channel function in neuropathic pain, was chaired by Troels Jensen Staehelin from Denmark.
Professor Staehelin presented a talk on: Can peripheral and central effects of sodium channels be tested in neuropathic pain? Professor Staehelin presented a putative precision medicine applied to sodium channels and elaborated on the developed thereof, including the interesting role of phenytoin. NaV 1.7 and 1.8 for instance are upregulated in neuronomas. How can we identify potential responders to sodium channels, was one of his key questions. He also adressed the question of application of lidocaine peripherally, whether this can reduce sensitization. Peripheral lidocain could reduce pain in some NP patients. Carbamazepin, also a sodium channel blocker (as dirty as phenytoin) might have better perspectives, according to a small study presented by the speaker.
Professor Katharina Zimmerman from Germany presented ‘Heat- and cold-resistant action potentials in nociceptors’ In the skin there are different phenotyipical populations of heat resistent nociceptors, and in totally the skin we vind mainly NaV 1.7, 1.8 and 1.9 , while centrally we find especially NaV 1.1, 1.2 and 1.6 isoforms. NaV 1.9. seems a key determinant for cold allodynia. NaV 1.8 knock out also reduces cold allodynia. Multiple isoforms therefore play a role in cold allodynia. Human Nav 1.8. however is much different from those on mice.
Simon Haroutounian from USA spoke about ‘pharmacological evidence of sodium channel targeted interventions’. He presented the rationale behind sodium channels in neuropathic pain and also on the locally delivering of NaV blockers for relieving neuropathic pain. He stipulated the effect of 2% lidocaine injecting in the peripheral system in a human paradigm, and could block evoked pain, cold-warm and pinpric pain, independent of QST profiling. Non selective blockade with lidocaine however, is not very convenient as it affects all nerve fibre functions, including motor function. To date there are no systemic sodium channel blockers evaluated in NP. However, some topical liposomal formulations of lidocaine derivatives might help to overcome some of these difficulties, however, not all. The speaker did point out the results with the NaV 1.7 blocker raxatrigine in NP, as well as the results of topical TV-45070 in postherpetic neuralgia. Both studies supported the sodium channel blocking route in a certain way, and the latter study supported the topical administration.
Goetenborg, 15-6-17, Jan M. Keppel Hesselink MD, PhD