Novel Therapies for the Treatment of Neuropathic Pain: Potential and Pitfalls

Abstract

Neuropathic pain affects more than one million people across the globe. The quality of life of people suffering from neuropathic pain has been considerably declining due to the unavailability of appropriate therapeutics. Currently, available treatment options can only treat patients symptomatically, but they are associated with severe adverse side effects and the development of tolerance over prolonged use. In the past decade, researchers were able to gain a better understanding of the mechanisms involved in neuropathic pain; thus, continuous efforts are evident, aiming to develop novel interventions with better efficacy instead of symptomatic treatment. The current review discusses the latest interventional strategies used in the treatment and management of neuropathic pain. This review also provides insights into the present scenario of pain research, particularly various interventional techniques such as spinal cord stimulation, steroid injection, neural blockade, transcranial/epidural stimulation, deep brain stimulation, percutaneous electrical nerve stimulation, neuroablative procedures, opto/chemogenetics, gene therapy, etc. In a nutshell, most of the above techniques are at preclinical stage and facing difficulty in translation to clinical studies due to the non-availability of appropriate methodologies. Therefore, continuing research on these interventional strategies may help in the development of promising novel therapies that can improve the quality of life of patients suffering from neuropathic pain.

Ion Channel Genes in Painful Neuropathies

“…While VGSCs play a crucial role in neuronal excitability and pain processing, alterations in these genes can only account for a portion of the complexity of PPN [7]. Recent studies have shown that other ICGs are involved in pain signaling, modulation, and transmission (Figure 1) [5,8,9]. This review delves into the growing function of ICGs in PPN, aside from VGSCs, which have been previously extensively discussed in recent reviews [7,10,11].…”

“…It is important to acknowledge that there is a correlation between pain perception and genetic variants in Ion Channel Genes (ICGs) [4]. As these ion channels play a critical role in generating, transmitting, and transforming nerve signals in the peripheral nerves, they must be thoroughly examined as promising molecular targets for PPN therapy [5]. Voltage-Gated Sodium Channels (VGSCs) are the most researched ICGs and have been linked to disorders such as congenital insensitivity to pain (CIP), paroxysmal extreme pain disorder (PEPD), erythromelalgia, small fiber neuropathy (SFN), and painful diabetic peripheral neuropathy (PDPN) [6].…”

A Review of the Therapeutic Targeting of SCN9A and Nav1.7 for Pain Relief in Current Human Clinical Trials

“…There are several associated problems that are manifested outside the challenges with pain. They include bowel 54 and urine problems, 59 palpitation (rapid heartbeats), 17 , 23 xerostomia (dry mouth), 60 keratoconjunctivitis sicca (dry eyes) 61 , and (hyperhidrosis) abnormal sweating. 54 Individuals with this condition suffer from orthostatic hypotension (when blood pressure drops suddenly upon standing) which can cause symptoms such as blurred vision, dizziness, and fainting.…”

Pain intensity and self‐perceived burden mediate the relationship between family functioning and pain catastrophizing in patients with neuropathic pain

“…Reports show that good family functioning positively reduces negative emotions (Dang et al, 2021), improves functioning in daily activities (Signs & Woods, 2020), and improves the quality of life (Zhang et al, 2022). Nevertheless, due to the lack of evidence on the relationship between family factors and pain outcomes (Shinu et al, 2022), there is a need to understand these relationships in patients with NP to provide ideas for their pain management.…”