Piromelatine exerts antinociceptive effect via melatonin, opioid, and 5HT1A receptors and hypnotic effect via melatonin receptors in a mouse model of neuropathic pain

Abstract

These data indicate that piromelatine is an effective treatment for both neuropathic pain and sleep disturbance in PSL mice. The antinociceptive effect of piromelatine is likely mediated by melatonin, opioid, and 5HT1A receptors; however, the hypnotic effect of piromelatine appears to be mediated by melatonin receptors.

Neuroprotective mechanism of the novel melatonin derivative Neu-P11 in brain ischemia related models

“…antinociceptive effects (19). Besides its neurological actions, Neu-P11 has demonstrated usefulness in reducing intraocular pressure (17).…”

Helicid alleviates pain and sleep disturbances in a neuropathic pain‐like model in mice

“…A partial nerve injury model was produced by tying a tight ligature with silk suture around, approximately from one‐third to half the diameter of the sciatic nerve on the ipsilateral side. The nerve of sham‐operated mice was exposed but not ligated (Liu et al ., ; Wang et al ., ). Both PSL‐ and sham‐operated mice were housed in separate cages to recover for at least 7 days before tests.…”

“…Mechanical allodynia was quantified by measuring hind paw withdrawal response (Liu et al ., ). Briefly, animals were placed in a clear test chamber with a framed metal mesh floor and allowed to habituate for 60 min prior to the test.…”

“…Under 5% chloral hydrate (360 mg kg −1 , i.p.) anaesthesia, mice that firstly underwent PSL surgery mentioned above were implanted with electrodes that consisted of two stainless steel screws (1 mm in diameter) and two Teflon‐coated, insulated stainless steel wires for polysomnographic electroencephalograms (EEG) and electromyogram (EMG) recordings at the same time according to our previous studies (Huang et al ., ; Liu et al ., ). After recovery for 10 days, mice were transferred to the recording chamber, and were given a 4‐day period of habituation.…”

“…In the present study, the effects of helicid on neuropathic pain and co‐morbid insomnia were evaluated in mice with partial sciatic nerve ligation (PSL), a model imitating neuropathic pain in humans (Liu et al ., ). In addition, we observed the expression of c‐Fos in the rostral (but not caudal) anterior cingulate cortex (rACC), which is implicated in encoding negative affective components of nociceptor stimulation (Johansen et al ., ; Qu et al ., ), and the ventrolateral preoptic area (VLPO) and the tuberomammillary nucleus (TMN), which play important roles in sleep–wake regulation, according to the ‘flip‐fop’ model to explore this mechanism (Lazarus et al ., ; Saper et al ., ).…”