Dimethyl Trisulfide Diminishes Traumatic Neuropathic Pain Acting on TRPA1 Receptors in Mice

Abstract

Pharmacotherapy of neuropathic pain is still challenging. Our earlier work indicated an analgesic effect of dimethyl trisulfide (DMTS), which was mediated by somatostatin released from nociceptor nerve endings acting on SST4 receptors. Somatostatin release occurred due to TRPA1 ion channel activation. In the present study, we investigated the effect of DMTS in neuropathic pain evoked by partial ligation of the sciatic nerve in mice. Expression of the mRNA of Trpa1 in murine dorsal-root-ganglion neurons was detected by RNAscope. Involvement of TRPA1 ion channels and SST4 receptors was tested with gene-deleted animals. Macrophage activity at the site of the nerve lesion was determined by lucigenin bioluminescence. Density and activation of microglia in the spinal cord dorsal horn was verified by immunohistochemistry and image analysis. Trpa1 mRNA is expressed in peptidergic and non-peptidergic neurons in the dorsal root ganglion. DMTS ameliorated neuropathic pain in Trpa1 and Sstr4 WT mice, but not in KO ones. DMTS had no effect on macrophage activity around the damaged nerve. Microglial density in the dorsal horn was reduced by DMTS independently from TRPA1. No effect on microglial activation was detected. DMTS might offer a novel therapeutic opportunity in the complementary treatment of neuropathic pain.

Investigation of the Role of the TRPA1 Ion Channel in Conveying the Effect of Dimethyl Trisulfide on Vascular and Histological Changes in Serum-Transfer Arthritis

“…Our study confirmed that DMTS is a potent agonist of TRPA1 channels [15,27]. We demonstrated that DMTS mitigated edema formation and plasma extravasation in the K/BxN serum-transfer arthritis model as well.…”

“…The control animals received nonarthritogenic BxN serum. DMTS (Sigma-Aldrich, Budapest, Hungary) solutions were prepared as described earlier [27]. The stock solution was prepared in dimethyl sulfoxide (Reanal, Budapest, Hungary; 1 mol/L), and was diluted 10× with saline containing polysorbate 80 (0.9% m/v NaCl and 2% v/v polysorbate 80; 100 mmol/L DMTS).…”

Correlation of TRPA1 RNAscope and Agonist Responses

“…Over the past years, the in situ hybridization-based technique RNAscope has been increasingly used in research and clinical studies due to its sensitivity and specificity, which have been evaluated in the context of pathologic diagnostics. 21 – 23 RNAscope has been used to evaluate TRPA1 and TRPV1 mRNA abundance in neuronal cells from the peripheral 24 – 26 and the central nervous system, 27 – 29 as well as non-neuronal tumor cells. 30 However, whether there is a correlation between mRNA and functional responses has not been assessed before.…”

Visual analysis of global research on the transient receptor potential ankyrin 1 channel: A literature review from 2002 to 2022

“…NP is defined by the International Association for the Study of Pain as “pain caused by a lesion or disease of the somatosensory nervous system” [ 86 ]. There is growing evidence that TRPA1 plays an important role in different patterns of NP progression, such as traumatic NP [ 87 ], chemotherapeutic-induced NP [ 88 ], and diabetic NP [ 89 ]. MicroRNAs (miRs) are small non-coding endogenous RNA molecules that inhibit their target mRNAs by binding complementarily in the informative 3′-UTR [ 90 ].…”