TRPV4 and TRPM8 as putative targets for chronic low back pain alleviation

Abstract

The purpose of this study is to investigate the presence of nervous fibers and expression of TRP channels in samples harvested during decompressive/fusion spine surgeries from patients affected by chronic low back pain (CLBP). The aim was to understand if members of this family of receptors played a role in detection and processing of painful stimuli, to eventually define them as potential targets for CLBP alleviation. Expression of transient receptor potential (TRP) channels (A1, V1, V2, V4, and M8) was evaluated in samples from different periarticular sites of 6 patients affected by CLBP, at both protein and transcript levels. The capsular connective pathological tissue appeared infiltrated by sensitive unmyelinated nervous fibers. An increase in TRP channel mRNAs and proteins was observed in the pathological capsule compared with tissues collected from the non-symptomatic area in five of the six analyzed patients, independently by the location and number of affected sites. In particular, TRPV4 and TRPM8 were consistently upregulated in pathological tissues. Interestingly, the only patient showing a different pattern of expression also had a different clinical history. TRPV4 and TRPM8 channels may play a role in CLBP and warrant further investigations as possible therapeutic targets.

Rs11726196 Single-Nucleotide Polymorphism of the Transient Receptor Potential Canonical 3 (TRPC3) Gene Is Associated with Chronic Pain

“…The TRPC3 channels, as well as other TRP channels (e.g., TRPV1, TRPV3, TRPV4, TRPA1, TRPM3, and TRPM8), possibly play an important role in nociception [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 26 ]. In humans, TRPC3 mRNA is highly expressed in the brain, including the cervical spinal cord and heart [ 32 ].…”

“…The antagonists of TRPV1, TRPV3, and TRPA1 have been advanced into clinical trials for the treatment of inflammatory, neuropathic, and visceral pain [ 20 ]. Additionally, TRPV4 and TRPM8 were reported to be involved in the mechanisms of chronic pain [ 23 , 24 ] and are suggested to be putative treatment targets for chronic low back pain [ 23 ]. For the TRPC channels, TRPC1, TRPC4, and TRPC5 are activated directly by inositol-1,4,5-trisphosphate, and TRPC3, TRPC6, and TRPC7 are activated by diacylglycerol (DAG), independent of the storage reduction of intracellular calcium [ 16 ].…”

TRPM8 Channels: Advances in Structural Studies and Pharmacological Modulation

“…TRP channels were also found in samples of patients with chronic low back pain, collected after decompressive/fusion spine surgeries. TRPM8 and TRPV4 channels were upregulated in these tissues in contrast to samples from non-symptomatic areas [106]. In cells carrying the Arg30Glu TRPM8 channel mutant, characteristic of familial trigeminal neuralgia, the increased response to menthol (1), was observed through Ca 2+ imaging and Patch-Clamp experiments, indicating that the TRPM8 gain-of-function contributes to pain in this pathology [107].…”

Chronic back pain as a spinal osteoarthritis manifestation: rationale and practice of symptomatic slow acting drugs for osteoarthritis use

“…Типично появление «стартовой» боли (усиление боли в момент начала движения и постепенное стихание впоследствии) и практически полное прекращение болевых ощущений при отдыхе, в положении сидя или лежа. Причиной появления механической боли могут быть выраженные структурные изменения при ОА ФС и ОА КПС, приводящие к нарушениям биомеханики, растяжению фасций и мышечному напряжению, ПС с вовлечением механорецепторов и активацией трансмембранных клеточных каналов, в частности TRPV [37][38][39].…”