Attenuating effect of mexiletine hydrochloride on herpetic pain in mice infected with herpes simplex virus

Abstract

The influence of mexiletine hydrochloride on herpes-related pain responses was examined using mice infected with herpes virus. BALB/c mice were inoculated with herpes simplex virus (HSV; 1 x 10(6) plaque-forming units) on the right hind paw, and the contralateral hind paw was without inoculation. The changes in nociceptive threshold were examined using electric von fray meter. BALB/c mice inoculated with HSV showed a decrease in nociceptive threshold. Intraperitoneal administration of mexiletine prevented the decrease in nociceptive threshold dose-dependently in HSV-inoculated mice, which was firstly observed at a dose of 15.0 mg kg(-1), and peaked at doses more than 17.5 mg kg(-1). This antinociceptive effect of mexiletine attained peaks at 60-90 min after administration and declined gradually to non-treated levels by 150 min. Intraperitoneal administration of mexiletine at a dose of 17.5 mg kg(-1) (but not 10.0 mg kg(-1)) caused significant increase in beta-endorphin levels in the mid brain and hypothalamus of HSV-inoculated mice. However, mexiletine scarcely affected noradrenaline (norepinephrine) levels in the pons and medulla oblongata, even when HSV-inoculated mice were treated with 17.5 mg kg(-1) mexiletine. These results strongly suggested that mexiletine exerts antinociceptive effects on herpes-related pain through enhancement of beta-endorphin levels in the central nervous system in HSV-inoculated mice. It is also suggested that mexiletine will be a good candidate for an antinociceptive drug in the treatment of acute herpetic pain in man.

Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in Dogs

“…Furthermore, anti-artemin therapy has been shown to be effective in preventing and reversing ongoing bladder hyperalgesia in an animal model of cystitis (DeBerry et al, 2015). In contrast, artemin exerts an antinociceptive effect on herpes-related pain by modulating the dynorphin levels in the central nervous system of HSV-inoculated mice (Asano et al, 2006). Based on this evidence, peripheral artemin is involved in generating pain signals in rodents.…”

Neurotrophic Factor Artemin Promotes Invasiveness and Neurotrophic Function of Pancreatic Adenocarcinoma In Vivo and In Vitro

“…Artemin elicits potential therapeutic effects on neural degeneration, injury, 18 and neurogenic pain. 19 However, Artemin functions as an oncogene that affects biological behaviors to promote the invasiveness of cancer cells 7 , 17 , 20 in many tumors, mediate the drug resistance of estrogen receptor-positive breast cancer cells, 8 and lower the sensitivity of endometrial cancer cells to taxol and doxorubicin. 21 These results suggested that the inhibition of Artemin could be a therapeutic target in several tumors.…”

Neurotrophins, endocannabinoids and thermo‐transient receptor potential: a threesome in pain signalling

“…Alternatively, Ret-independent signalling appears mediated by NCAM/GFRa3 through activation of Fyn kinase, which sensitises small-diameter sensory neurons by potentiating TRPV1 activity (Bespalov et al, 2011;Schmutzler et al, 2011). Additionally, artemin has also been shown to display anti-nociceptive activity in neuropathic pain models (Gardell et al, 2003;Asano et al, 2006;Yoshida et al, 2011). It has been reported that artemin may produce anti-nociception, at least in part by attenuating the channel activity of the TRPA1 channel (Yoshida et al, 2011).…”