Antinociceptive Effects of Isosakuranetin in a Rat Model of Peripheral Neuropathy

Abstract

Chronic pain remains a challenging clinical reality, yet currently available analgesics are insufficient to meet clinical needs. Increasing attention has been paid to bioactive compounds from natural plants, which may be efficacious against pain. This study examined the antinociceptive effects of isosakuranetin, a plant-derived transient receptor potential melastatin 3 blocker, in a rat model of peripheral neuropathy. Adult male Sprague-Dawley rats were first allowed to go through the chronic constriction injury surgery to develop neuropathic pain. They were then treated with isosakuranetin (1.5, 3, or 6 mg/kg) intraperitoneally and the effects on mechanical, thermal, and cold hyperalgesia were assessed using the von Frey filament test, Hargreaves' plantar test, and cold plate test, respectively. Isosakuranetin dose-dependently alleviated mechanical, thermal, and cold hyperalgesia and the antinociceptive potency was similar across the assays. In the rotarod test, isosakuranetin did not significantly affect motor performance within the doses tested, confirming the antinociceptive specificity. In summary, these findings suggest that isosakuranetin may be useful in treating neuropathic pain and deserves further investigation.

Functional expression and pharmacological modulation of TRPM3 in human sensory neurons

“…In recent years, research in rodents has revealed that the cation channel TRPM3 plays a central role in the somatosensory pathway, where it is involved in acute noxious heat sensing and in the development of inflammatory hyperalgesia (Behrendt, ; Vriens et al, ). Moreover, pharmacological inhibition of TRPM3 alleviates pain in a variety of preclinical models in mice and rats (Jia et al, ; Krugel et al, ; Straub et al, ), highlighting the potential of TRPM3 as a target for novel analgesic drugs (Held, Voets, & Vriens, ). However, whether TRPM3 is implicated in somatosensation and pain in humans remains unknown.…”

“…In mouse, TRPM3 is expressed in approximately 60% of somatosensory neurons and plays a central role in the detection of noxious heat (Vriens et al, ). Strikingly, TRPM3 −/− mice do not develop inflammatory hyperalgesia in response to injection of complete Freud's adjuvant (Vriens et al, ) and systemic TRPM3 antagonists were shown to alleviate mechanical and thermal hyperalgesia in mouse and rat models of inflammatory and neuropathic pain (Chen, Chen, Qian, Fang, & Zhu, ; Jia, Zhang, & Yu, ; Krugel, Straub, Beckmann, & Schaefer, ). Moreover, TRPM3 activity in sensory neurons is strongly suppressed by μ‐opioid receptor activation in sensory neurons, suggesting that TRPM3 may contribute to peripheral analgesic effects of opioids (Dembla et al, ; Quallo, Alkhatib, Gentry, Andersson, & Bevan, ; Yudin & Rohacs, ).…”

RETRACTED ARTICLE: Ultra-diluted Toxicodendron pubescens attenuates pro-inflammatory cytokines and ROS- mediated neuropathic pain in rats

“…Raised oxidative stress, increased vascular permeability and release of different inflammatory mediators including substance P and calcitonin gene related peptide produced by nociceptive terminals, formation and/or release of bradykinin, prostaglandins, growth factors and cytokines leads to the occurrence of neuropathic pain 7 . Recently, the anti-inflammatory and antioxidant agents like N-acetyl carnitine and alpha lipoic acid are being investigated as add-on medications for the management of neuropathic pain 8 .…”

“…Evidence based surveys have revealed that patients with chronic pain prefer to use herbal treatments for these painful conditions 11 , 12 . Several pre-clinical and clinical studies have reported the beneficial effect of medicinal plants in the therapy of painful neuropathy 4 , 8 , 13 – 17 . Toxicodendron pubescens P. Mill belonging to family anacardiaceae is known as Rhus toxicodendron or Rhus tox (RT) in alternative medicines 18 , 19 .…”

Heat sensing involves a TRiPlet of ion channels

“…In this respect, TRPA1 and TRPM3 may potentially be safer targets. Indeed, antagonists of TRPA1 and TRPM3 did not affect core body temperature in preclinical studies (Chen et al, ; Jia, Zhang, & Yu, ; Straub et al, ), and heat withdrawal latencies were only marginally altered in DKO M3/A1 mice (Vandewauw et al, ). We expect that further preclinical and clinical studies will reveal whether pharmacological modulators of these channels can be developed as novel weapons in the battle against pain.…”