Rosmarinic acid attenuates development and existing pain in a rat model of neuropathic pain: An evidence of anti-oxidative and anti-inflammatory effects.
We aimed to investigate the potential prophylactic and curative effects of rosmarinic acid, one of the main constituents of rosemary, on the neuropathic pain induced by chronic constriction injury (CCI) in rats.
CCI was used to induce peripheral neuropathic pain. In prophylactic groups, rosmarinic acid (10, 20, and 40 mg/kg, i.p.) was administered from the day of surgery (day 0) for 14 days. In treatment group, rosmarinic acid (40 mg/kg) was given from day 5 (after the pain was established), for 7 days. The degree of mechanical allodynia, cold allodynia, and heat hyperalgesia were measured on days 0, 3, 5, 7, 10 and 14 post-surgery. The open field test was carried out to assess locomotor activity of animals. Lumbar spinal cord levels of astroglia activation marker, glial fibrillary acidic protein (GFAP), microglial activation marker, ionized calcium-binding adapter molecule 1 (Iba-1), toll-like receptor 4 (TLR-4), tumor necrosis factor alpha (TNF-α), inducible isoform of nitric oxide synthase enzyme (iNOS) and apoptotic factors were quantified via western blot on days 7 and 14.
CCI rats showed a significant mechanical allodynia, cold allodynia and thermal hyperalgesia, compared to sham ones on day 3, persisted up to day 14 post-CCI. Rosmarinic acid was able to prevent and also attenuate CCI-induced behavioral features in prophylactic as well as treatment groups, respectively. A significant increase in the levels of TNF-α, iNOS, apoptotic factors (Bax, caspases 3, 9), Iba-1, TLR-4, and GFAP was observed on both days 7 and 14, which was suppressed by 14 days administration of rosmarinic acid.
These findings further support the use of rosemary in traditional medicine to alleviate pain. Rosmarinic acid could be a promising compound in prophylaxis and treatment of neuropathic pain. Anti-apoptotic and anti-inflammatory effects of rosmarinic acid may have important roles in the observed antinociceptive properties.
Rahbardar MG
，Amin B
，Mehri S
，Mirnajafi-Zadeh SJ
，Hosseinzadeh H
... -
《-》
Antiallodynic effect induced by [6]-gingerol in neuropathic rats is mediated by activation of the serotoninergic system and the nitric oxide-cyclic guanosine monophosphate-adenosine triphosphate-sensitive K(+) channel pathway.
The present study evaluated the possible antiallodynic effect induced by [6]-gingerol in rats with L5-L6 spinal nerve ligation (SNL). Moreover, we determined the possible mechanism underlying the antiallodynic effect induced by [6]-gingerol in neuropathic rats. The animals underwent L5-L6 SNL for the purpose of developing tactile allodynia. Tactile allodynia was measured with von Frey filaments. Intrathecal administration of [6]-gingerol reversed SNL-induced tactile allodynia. The [6]-gingerol-induced antiallodynic effect was prevented by the intrathecal administration of methiothepin (30 μg per rat; nonselective 5-hydroxytryptamine [5-HT] antagonist), WAY-100635 (6 μg per rat; selective 5-HT1A receptor antagonist), SB-224289 (5 μg per rat; selective 5-HT1B receptor antagonist), BRL-15572 (4 μg per rat; selective 5-HT1D receptor antagonist), and SB-659551 (6 μg per rat; selective 5-HT5A receptor antagonist), but naloxone (50 μg per rat; nonselective opioid receptor antagonist) did not prevent the [6]-gingerol-induced antiallodynic effect. Moreover, intrathecal administration of Nω-nitro-l-arginine methyl ester (100 μg per rat; nonselective nitric oxide [NO] synthase inhibitor), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 μg per rat; inhibitor of guanylate cyclase), and glibenclamide (50 μg per rat; channel blocker of adenosine triphosphate [ATP]-sensitive K+ channels) prevented the [6]-gingerol-induced antiallodynic effect. These data suggest that the antiallodynic effect induced by [6]-gingerol is mediated by the serotoninergic system involving the activation of 5-HT1A/1B/1D/5A receptors, as well as the NO-cyclic guanosine monophosphate-ATP-sensitive K+ channel pathway but not by the opioidergic system.
Mata-Bermudez A
，Izquierdo T
，de Los Monteros-Zuñiga E
，Coen A
，Godínez-Chaparro B
... -
《-》
The role of spinal serotonin receptor and alpha adrenoceptor on the antiallodynic effects induced by intrathecal milnacipran in chronic constriction injury rats.
Milnacipran, a reuptake inhibitor of noradrenaline (NA) and serotonin (5-HT), elicits an antiallodynic effect in rats with neuropathic pain; however, the role of NA and 5-HT receptors in the induction of the antiallodynic effect of milnacipran remains unclear. Thus, we examined the effects of prazosin as an α1 adrenoceptor antagonist, yohimbine as an α2 adrenoceptor antagonist, metergoline as a 5-HT1, 5-HT2 and 5-HT7 receptor antagonist, cyanopindolol as a 5-HT1A/1B receptor antagonist, ketanserin as a 5-HT2 receptor antagonist, and ondansetoron as a 5-HT3 receptor antagonist on the antiallodynic effect of milnacipran in neuropathic rats with chronic constriction injury (CCI). The CCI rats expressed mechanical and thermal allodynia, which was attenuated by intrathecal injection of milnacipran. Yohimbine, but not prazosin, reversed the milnacipran-induced antiallodynic effect. The antiallodynic effect of milnacipran was also reversed by metergoline, ketanserin and ondansetron, while cyanopindolol reversed the antiallodynic effect on mechanical, but not thermal stimulation. Furthermore, c-Fos expression in lamina I/II of the spinal dorsal horn was enhanced by thermal stimulation and the enhanced expression of c-Fos was suppressed by milnacipran. This effect of milnacipran was reversed by yohimbine, metergoline, katanserin and ondansetron, but not prazosin. These results indicate that the effect of milnacipran on mechanical and thermal allodynia and c-Fos expression is elicited through the α2 adrenoceptor, but not α1 adrenoceptor, and 5-HT2 and 5-HT3 receptors; furthermore, the 5-HT1A/1B receptor is involved in mechanical allodynia, but not thermal allodynia.
Nakamura T
，Ikeda T
，Takeda R
，Igawa K
，Naono-Nakayama R
，Sakoda S
，Nishimori T
，Ishida Y
... -
《-》
Sex-dependent antiallodynic effect of α(2) adrenergic receptor agonist tizanidine in rats with experimental neuropathic pain.
The purpose of this study was to investigate the mechanism of antiallodynic effect of tizanidine in neuropathic rats. Spinal nerve ligation reduced withdrawal threshold which was interpreted as tactile allodynia. Increasing doses of tizanidine induced a dose-dependent antiallodynic effect in nerve injured rats. Tizanidine was more effective in female than male neuropathic rats. This drug induced a lower antiallodynic effect in ovariectomized, compared with non-ovariectomized, neuropathic rats, while systemic reconstitution of estradiol (E2) levels in ovariectomized neuropathic females fully restored the antiallodynic effect of tizanidine. Naloxone reduced the antiallodynic effect of tizanidine in male but not in female neuropathic rats. Ovariectomy restored the antagonizing effect of naloxone in the antiallodynic effect of tizanidine, whereas treatment with E2 abolished the effect of naloxone on tizanidine activity. Rauwolscine (α2 antagonist) and imiloxan (α2B antagonist) completely abated tizanidine-induced antiallodynic effect in female neuropathic rats. In contrast, BRL-44408 (α2A antagonist) partially decreased the effect of tizanidine while JP-1302 (α2C antagonist) was ineffective. Rauwolscine, imiloxan and BRL-44408 decreased withdrawal threshold in naïve female rats. Rauwolscine did not modify withdrawal threshold in naïve male rats. AGN192403 (I1 antagonist), BU224 (I2 antagonist), prazosin (α1 antagonist) and methiothepin (5-HT antagonist) did not modify tizanidine-induced antiallodynia in neuropathic females and males. These data indicate that tizanidine exhibits a sex-dependent antiallodynic effect in neuropathy. Data also suggest that activation of adrenergic α2B and α2A and opioid receptors participate in the antiallodynic effect of tizanidine in female and male, respectively, neuropathic rats.
Rodríguez-Palma EJ
，Castelo-Flores DG
，Caram-Salas NL
，Salinas-Abarca AB
，Centurión D
，De la Luz-Cuellar YE
，Granados-Soto V
... -
《-》
ResearchGate
(全网免费下载)
钛学术
(全网免费下载)
