TRP Channels Role in Pain Associated With Neurodegenerative Diseases

Abstract

Transient receptor potential (TRP) are cation channels expressed in both non-excitable and excitable cells from diverse tissues, including heart, lung, and brain. The TRP channel family includes 28 isoforms activated by physical and chemical stimuli, such as temperature, pH, osmotic pressure, and noxious stimuli. Recently, it has been shown that TRP channels are also directly or indirectly activated by reactive oxygen species. Oxidative stress plays an essential role in neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases, and TRP channels are involved in the progression of those diseases by mechanisms involving changes in the crosstalk between Ca 2+ regulation, oxidative stress, and production of inflammatory mediators. TRP channels involved in nociception include members of the TRPV, TRPM, TRPA, and TRPC subfamilies that transduce physical and chemical noxious stimuli. It has also been reported that pain is a complex issue in patients with Alzheimer's and Parkinson's diseases, and adequate management of pain in those conditions is still in discussion. TRPV1 has a role in neuroinflammation, a critical mechanism involved in neurodegeneration. Therefore, some studies have considered TRPV1 as a target for both pain treatment and neurodegenerative disorders. Thus, this review aimed to describe the TRP-dependent mechanism that can mediate pain sensation in neurodegenerative diseases and the therapeutic approach available to palliate pain and neurodegenerative symptoms throughout the regulation of these channels.

Manmade Electromagnetic Fields and Oxidative Stress—Biological Effects and Consequences for Health

“…Studies on mechanisms such as those related to calcium channels are particularly informative as calcium concentration-dependent cellular responses may result in a multitude of pleiotropic effects [ 9 ]. Voltage-gated calcium channels were shown to be activated by nonthermal pulse-modulated 27 MHz RF-EMF, leading to an increase in NO [ 108 ] while nonselective calcium channels such as transient receptor potential (TRP) channels are activated by oxidative stress [ 109 , 110 ]. For instance, the TRPV1 channel, belonging to the calcium-permeable TRP superfamily, can be activated not only by stimuli such as heat and capsaicin, but also by oxidative stress.…”

“…Activation of TRPV channels by oxidative stress/EMF was demonstrated to result in an increase in neuronal calcium concentrations that may lead to physiological changes and pathological processes such as apoptosis [ 43 , 111 , 112 ]. The occurrence of TRPV1 is particularly high in neurons of the hippocampus and in spinal ganglia, where it is probably involved in the transmission of pain, which is impaired in neurodegenerative processes [ 109 , 110 ].…”

Genome-wide contribution of common Short-Tandem Repeats to Parkinson’s Disease genetic risk

“…PART1 is a long non-coding RNA that was found to be differentially expressed (downregulated) in a microarray-based analysis of 50 PD patients compared to 22 healthy controls 29 . The ZSWIM7 eSTR was associated with significant effects on gene expression in different genes, such as TRPV2, a cation channel part of the Transient receptor potential family of proteins (TRPs) that are activated by physical and chemical stimuli 30 , and that are known to be involved in the regulation of ionic homeostasis, which is disrupted in PD 31 ; ADORA2B is an adenosine receptor which has been associated with neurodegenerative conditions such as Huntington's disease 32 , however no link to PD has been established so far; lnc-NCOR1-1 and NCOR1 (Nuclear Receptor Corepressor 1) are located within the same chromosomal region (short arm of chromosome 17) and were also influenced by the eSTRs. The former long non-coding gene has not been thoroughly characterized, therefore little is known about its function.…”

Cognitive Impairment and Dementia: Gaining Insight through Circadian Clock Gene Pathways

“…Cognitive disorders, such as dementia with AD, raise this bar even further since disorders such as AD are multifactorial in origin. Multiple mechanisms may lead to cognitive impairment and involve cellular injury from β-amyloid (Aβ), tau, excitotoxicity, metabotropic receptors, lipid dysfunction, mitochondrial damage, acetylcholine loss, astrocytic cell injury, oxidative stress, heavy metal disease, and cellular metabolic dysfunction with diabetes mellitus (DM) [3,4,8,14,27,[35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54]. Present strategies to treat cognitive loss with AD involve therapy with cholinesterase inhibitors that may decrease some symptoms but do not alter disease progression [11,15,52,55].…”