An integrated review on new targets in the treatment of neuropathic pain

Abstract

Neuropathic pain is a complex chronic pain state caused by the dysfunction of somatosensory nervous system, and it affects the millions of people worldwide. At present, there are very few medical treatments available for neuropathic pain management and the intolerable side effects of medications may further worsen the symptoms. Despite the presence of profound knowledge that delineates the pathophysiology and mechanisms leading to neuropathic pain, the unmet clinical needs demand more research in this field that would ultimately assist to ameliorate the pain conditions. Efforts are being made globally to explore and understand the basic molecular mechanisms responsible for somatosensory dysfunction in preclinical pain models. The present review highlights some of the novel molecular targets like D-amino acid oxidase, endoplasmic reticulum stress receptors, sigma receptors, hyperpolarization-activated cyclic nucleotide-gated cation channels, histone deacetylase, Wnt/β-catenin and Wnt/Ryk, ephrins and Eph receptor tyrosine kinase, Cdh-1 and mitochondrial ATPase that are implicated in the induction of neuropathic pain. Studies conducted on the different animal models and observed results have been summarized with an aim to facilitate the efforts made in the drug discovery. The diligent analysis and exploitation of these targets may help in the identification of some promising therapies that can better manage neuropathic pain and improve the health of patients.

Transcriptional Profiling of Non-injured Nociceptors After Spinal Cord Injury Reveals Diverse Molecular Changes

“…Synaptogenesis is typically associated with developmental processes, including axon guidance and synapse formation (Klein, 2004;Price and Inyang, 2015). However, activation of various signaling pathways involved in synaptogenesis may also contribute to pain; for example persistent pain is supported via changes in synaptic signaling, neuronal plasticity, and long term potentiation, and may form memory-like networks for painful signals that allow persistent pain to occur long after the initial injury (Kobayashi et al, 2007;Khangura et al, 2019).…”

“…The gene transcript is part of the Ephrin tyrosine kinase receptor protein family that is expressed in laminae I-III of the spinal dorsal horn on small and medium-sized DRG neurons (presumably nociceptors; Bundesen et al, 2003). Ephb receptors regulate synaptic activity in the spinal cord and contribute to persistent pain associated with NMDA activity (Khangura et al, 2019). Numerous receptor tyrosine kinases localize to synapses and contribute to synaptogenesis in addition to EphB receptors, including Trk receptors (Biederer and Stagi, 2008).…”

NeuroHeal Treatment Alleviates Neuropathic Pain and Enhances Sensory Axon Regeneration

“…It is characterized by the appearance of spontaneous pain, dysesthesia, hyperalgesia, and allodynia. Neuropathic pain after PNI is characterized by changes in dorsal root ganglia (DRG) and dorsal horn neurons excitability, which are followed by the disturbance of the normal function of other central nervous areas such as thalamic relay nuclei, somatosensory cortex, amygdala, and others [4][5][6]. Nonetheless, despite the…”

Are painDETECT scores in musculoskeletal disorders associated with duration of daily pain and time elapsed since current pain onset?

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