According to the International Association for the Study of Pain, neuropathic pain (NP) is pain that arises from lesions and/or disease of the somatosensory system. NP is a global health problem that is quite costly to treat. Two treatment options that have been used to treat NP are interventional pain management (IPM) and peripheral nerve stimulation (PNS). IPM includes diagnostic/therapeutic procedures administered through the skin that aim to modify pain signals in the body. Unlike other treatments of NP, like spinal cord stimulation, thus far there are no clear guidelines outlining the role and usage of PNS for NP treatment. UTCSP investigator Dr. Anuj Bhatia and colleagues surveyed international pain experts to investigate the current perception surrounding the use of IPM and PNS as treatments for NP.

A cross-sectional online survey was circulated to NP experts worldwide (pain medicine physicians, researchers, and leaders of professional pain societies). Of the 24 that responded, the most targeted areas using PNS were the distal common peroneal tibial and the sural nerves (60%). Overall, the aggregate reported NP treatment order was 1) non-opioid medications, 2) IPM which included epidural/perineural steroid injections and transcutaneous electrical nerve stimulation 3) pulse radiofrequency (RF) or RF ablation/denervation, 4) temporary PNS then permanent PNS. Half of the respondents (50%) reported that they preferred to trial non-neuromodulation treatments for 1-3 months before considering PNS. The majority of respondents (92%) believe that PNS should be administered early on in treatment plans for NP. The most common barriers reported for the use of PNS were high costs, lack of evidence supporting its usage, little to no proper training programs, and overall insufficient familiarity with the treatment.

This over-arching and broad survey is a steppingstone towards further understanding the opinions, pros and cons surrounding PNS as a treatment option for NP. However, it is clear that there still needs to be more research towards understanding PNS and the outcomes of this treatment.

This over-arching and broad survey is a steppingstone towards further understanding the opinions, pros and cons surrounding PNS as a treatment option for NP.

Current treatments for chronic pain tend to conceal and dampen nociceptive processing rather than target its root causes. Many forms of chronic pain are thought to involve sensitization of spinal pain networks. Sensitization of nociceptive pathways shares several mechanisms with the strengthening of neuronal pathways in the brain which gives rise to memory. Like memory traces in the brain, it has previously been shown that sensitized nociceptive pathways can be destabilized and modified upon reactivation. However, the cellular mechanisms underlying the destabilization of ‘pain memory traces’ in the spinal cord are poorly understood. UTCSP member Dr. Rob Bonin and his colleagues performed a battery of behavioural, molecular, and electrophysiological experiments in mice to study the cellular mechanisms involved in the reversal of pain hypersensitivity.

To selectively reverse mechanical hypersensitivity in commonly used mouse models of pain, the authors of this study leveraged parallels between pain and memory by focusing on a nonionotropic form of NMDA receptor-mediated signaling involved in the weakening of synaptic connections in the brain. They found that reactivating sensitized sensory pathways, while pharmacologically inducing nonionotropic NMDA receptor activity, reverses mechanical hypersensitivity. Similarly, potentiated spinal cord pathways can be reactivated and weakened ex vivo by nonionotropic NMDA receptor activity. The authors identified specific synaptic proteins that are degraded to reduce mechanical hypersensitivity upon reactivation, many of which are also degraded during memory modification.

The results of this study published in Science Advances reveal a unique signaling pathway which enables reversal of pathological pain in mice by targeting its underlying cellular causes. Ultimately, gaining a better understanding of the dynamic regulation of pathological pain could lead to new therapeutic options for treating chronic pain conditions in humans.

The results of this study published in Science Advances reveal a unique signaling pathway which enables reversal of pathological pain in mice by targeting its underlying cellular causes.