Research Paper on By enhancing glycine-mediated spinal neurotransmission and decreasing central nociceptive signaling, inhibition of glycine re-uptake may be a useful method for treating pain.

Description

Title: By enhancing glycine-mediated spinal neurotransmission and decreasing central nociceptive signaling, inhibition of glycine re-uptake may be a useful method for treating pain.

Abstract: Disinhibition of spinal cord nociceptive signaling to higher cortical centers is one of the numerous cellular and molecular processes that have been linked to pathological pain. Importantly, the evidence points to impaired glycinergic neurotransmission as a key maladaptive mechanism causing mechanical hyperalgesia and allodynia in the dorsal horn of the spinal cord in inflammatory and neuropathic pain models. Therefore, it has been proposed that pharmacological substances that can increase glycinergic tone in the dorsal horn may be able to reduce or stop abnormal nociceptor signaling to the brain and act as a novel class of analgesics for a variety of pathological pain states. In fact, there is a lot of interest in drugs that improve dysfunctional glycinergic transmission, especially inhibitors of the glycine transporters (GlyT1 and GlyT2). These drugs have the potential to be a new class of analgesics. It has been suggested that inhibiting the GlyTs, which are Na+/Cl-dependent solute carrier 6 (SLC6) transporters, could increase spinal extracellular glycine concentrations and improve GlyR-mediated inhibitory neurotransmission in the dorsal horn. In several preclinical models of acute and chronic pain, a variety of GlyT1 and GlyT2 inhibitors have shown widespread analgesic efficacy, offering hope for the strategy to deliver a first-in-class non-opioid analgesic with a mechanism of action different from current standard of care. This review will highlight the therapeutic potential of GlyT inhibitors as a novel class of analgesics, present recent advances in the field, and talk about the major difficulties in turning a GlyT inhibitor into a painkiller that is both safe and effective.

Keywords: glycine; GABA; glycine transporter (GlyT); glycine receptor (GlyR); nociceptor; N-methyl- D-aspartate (NMDA) receptor; spinal cord; dorsal horn; hyperalgesia; allodynia; inflammatory pain; neuropathic pain

Paper Quality: SCOPUS / Web of Science Level Research Paper

Subject: Biomolecules

Writer Experience: 20+ Years

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