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Pain highlights: August.

The relative contribution of peripheral versus central mechanisms to chronic neuropathic pain following peripheral nerve injury has been a long-standing debate. A couple of important papers were published this month, which illustrate the different roles for played by various peripheral nerve subtypes.

Laiche Djouhri, from Sally Lawson’s lab in Bristol studied rats with partial nerve ligations. It’s commonly thought that one of the main mechanisms of chronic pain in nerve lesions arises from central (dorsal horn and higher) plasticity following loss of input from the Wallerian degeneration of axotomised peripheral neurons. Djourhi et al show that the nerves that survive might be just as important. They show that C-, Ad-, and Ab-nociceptors all display abnormal activity including spontaneous abnormal firing, abnormal thresholds and altered membrane dynamics. This suite of abnormal signaling in intact neurons seems likely to contribute to the diverse sensations that patients report following nerve injury. 

However, what is still not clear to what extent this activity might be responsible for the maintenance of chronic pain, beyond the precipitating injury. Ayano Nakao from Fusao Kato’s lab in Jikei University show that TRPV1 expressing c-fibre’s may have a specific role in the central pathogensis of neuropathic pain. They show that ablating c-fibres with post-natal capsaicin has little effect on mechanical allodynia induced by spinal nerve ligation. However, they observe significant reduction in the potentiation of the connectivity between lateral parabrachial nucleus and capsular portion of the central nucleus of the amygdala (a major downstream pathway for lamina 1 dorsal horn neurons that receive c-fibre inputs from the periphery). This shows that this pathway seems to be specifically dependent on c-fibre integrity. It also highlights the need to understand exactly what specific aspects of pain behaviour is mediated by the parabrachial-amygdala pathway -  a question that could be addressed by neuroimagers.  

Finally, on a more clinical note, evidence for what may be a new chronic pain disorder was published in Neurology this month. Christopher Klein and colleagues at the Mayo clinic have discovered that pain is commonly associated with voltage-gated potassium channel (VGKC) autoimmunity. VGKC autoimmunity has been one of the most interesting new chapters in neurology in the last decade – with a spectrum of clinical disorders spanning peripheral motor nerve hyperexcitability, neuromyotonia and most recently, limbic encephalitis and psychosis. Klein et al reviewed the cases of positive VGKC assays who had been neurologically assessed, and found a large number of patients with pain as an isolated phenomenon. Typical features were neuropathic and nociceptive (and often misdiagnosed as psychogenic pain or fibromyalgia), and pain was often accompanied with associated features such as abnormal sweating and thermal sensation – consistent with peripheral nociceptor hyperexcitability. Sera was subtyped positive for LGI1-IgG and CASPR2-IgG. Importantly, pain often resolved with immunotherapy. This defines a new and treatable clinical pain syndrome, and as word gets out and pain neurologists start sending of the antibodies, may turn out to be more common than previously thought (as was the case with VGKC encephalitis).  


Laiche Djouhri, Xin Fang, Stella Koutsikou, Sally N. Lawson. Partial nerve injury induces electrophysiological changes in conducting (uninjured) nociceptive and nonnociceptive DRG neurons: Possible relationships to aspects of peripheral neuropathic pain and paresthesias. Pain. 153 (2012) 1824–1836. 

Ayano Nakao, Yukari Takahashi, Masashi Nagase, Ryo Ikeda, Fusao Kato. Role of capsaicin-sensitive C-fiber afferents in neuropathic pain-induced synaptic potentiation in the nociceptive amygdala. Molecular Pain 2012, 8:51

Christopher J. Klein, Vanda A. Lennon, Paula A. Aston, Andrew McKeon, Sean J. Pittock. Chronic pain as a manifestation of potassium channel-complex autoimmunity. Neurology. Published online before print August 15, 2012

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Thanks for the content, looking forward for more articles.

January 4, 2013 | Unregistered CommenterTENDINTIS

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