Search

Highlights • Oral administration of sinomenine attenuates formalin-induced nociceptive behavior. • Oral administration of sinomenine inhibits ERK activation induced by intra plantar injection of formalin in spinal cord. • The analgesic effect of sinomenine may be evoked by μ-opioid receptors. Abstract Sinomenine, an alkaloid originally isolated from the roots and the rhizome of Sinomenium acutum is used as a traditional Chinese herbal medicines for rheumatoid arthritis and neuralgia. The aims of this study were to investigate the effects of oral administration of shinomenine on formalin-induced nociceptive behavior in mice and the opioid receptor subtypes involved in the antinociceptive effects of sinomenine. Our findings showed that a single dose of oral-administrated sinomenine inhibited the formalin induced licking and biting responses in a dose-dependent manner. Intraperitoneal pretreatment with naloxone hydrochloride, an opioid receptor antagonist, and β-funaltrexamine hydrochloride (β-FNA), a selective μ-opioid receptor antagonist, significantly attenuated sinomenine induced antinociception, but not by naltrindole, a nonselective δ-opioid receptor antagonist and nor-binaltorphimine, a selective κ-opioid receptor antagonist. Furthermore, in western blot analysis, oral administration of sinomenine resulted in a significant blockage of spinal extracellular signal-regulated protein kinase (ERK1/2) activation induced by formalin. Naloxone hydrochloride and β-FNA significantly reversed the blockage of spinal ERK1/2 activation induced by sinomenine. These results suggest that sinomenine-induced anti nociceptive effect and blockage of spinal ERK1/2 activation may be triggered by activation of μ-opioid receptors. [ABSTRACT FROM AUTHOR]

Highlights • Intraplantar injection of BEO attenuates allodynia induced by PSNL. • Intraplantar injection of BEO inhibits ERK activation induced by PSNL in the lumbar dorsal spinal cord. • The analgesic effect of BEO may be evoked by μ-opioid receptors. Abstract The essential oil of bergamot (BEO) is one of the most common essential oils and is most familiar to the general public. The aims of this study were to investigate the effect of intraplantar (i.pl.) BEO on neuropathic allodynia induced by partial sciatic nerve ligation (PSNL) in mice and the opioid receptor subtypes involved in the antiallodynic effects of BEO. Our findings showed that a single dose of i.pl. administration of BEO significantly inhibited the PSNL-induced neuropathic pain using the von Frey test. The i.pl pretreatment with naloxone methiodide, a peripherally acting μ-opioid receptor preferring antagonist, β-funaltrexamine hydrochloride (β-FNA), a selective μ-opioid receptor antagonist, and β -endorphin antiserum significantly reversed the antiallodynic effect of BEO in the von Frey test, but not by naltrindole, the nonselective δ-opioid receptor antagonist and nor-binaltorphimine, the selective κ-opioid receptor antagonist. Furthermore, in the western blotting analysis, i.pl. administration of BEO resulted in a significant blockage of spinal extracellular signal-regulated protein kinase (ERK) activation induced by PSNL. Naloxone methiodide and β-FNA significantly reversed the blockage of spinal ERK activation induced by BEO. These results suggest that i.pl. injection of BEO-induced antiallodynic effect and blockage of spinal ERK activation may be triggered by activation of peripheral μ-opioid receptors. [ABSTRACT FROM AUTHOR]

Intrathecal (i.t.) injection of morphine-3-glucuronide (M3G), a major metabolite of morphine without analgesic actions, produces severe hindlimb scratching followed by biting and licking in mice. The M3G-induced behavioral response was inhibited dose-dependently by pretreatment with an antisera against dynorphin. However, the selective κ -opioid receptor antagonist, nor-BNI did not prevent the M3G-induced behavioral response. Dynorphin is rapidly degraded by a dynorphin-converting enzyme (cystein protease), to leucine-enkephalin (Leu-ENK). The M3G-induced behavioral response was inhibited dose-dependently by pretreatment with the antisera against Leu-ENK. We also showed that M3G co-administered with Leu-ENK-converting enzyme inhibitors, phosphoramidon and bestatin produced much stronger behavioral responses than M3G alone. Furthermore, the M3G-induced behavioral responses were inhibited dose-dependently by i.t. co-administration of the non-selective δ -opioid receptor antagonist, naltrindole or the selective δ 2 -opioid receptor antagonist, naltriben, whereas the selective δ 1 -opioid receptor antagonist, BNTX had no effect. An i.t. injection of M3G also produced a definite activation of ERK in the lumbar dorsal spinal cord. Western blotting analysis revealed that antisera against dynorphin, antisera against Leu-ENK, naltrindole or naltriben resulted in a significant blockade of ERK activation induced by M3G in the spinal cord. Taken together, these results suggest that M3G-induced nociceptive responses and ERK activation may be triggered via δ 2 -opioid receptors activated by Leu-ENK, which is formed from dynorphin in the spinal cord. [ABSTRACT FROM AUTHOR]

Highlights: [•] Nociceptive behavior was not observed in mice treated with i.t. Leu-ENK alone. [•] Leu-ENK co-injected with peptidase inhibitors evoked nociceptive behaviors. [•] Leu-ENK co-injected with peptidase inhibitors evoked activation of spinal ERK2. [•] The nociceptive behavioral response was evoked through spinal δ 2-opioid receptor. [Copyright &y& Elsevier]

Abstract: Nociceptin/orphanin FQ (N/OFQ), the endogenous ligand for the N/OFQ peptide (NOP) receptors, has been shown to be metabolized into some fragments. We examined to determine whether intrathecal (i.t.) N/OFQ (1–13), (1–11) and (1–7) have antinociceptive activity in the pain-related behavior after intraplantar injection of capsaicin. The i.t. administration of N/OFQ (0.3–1.2nmol) produced an appreciable and dose-dependent inhibition of capsaicin-induced paw-licking/biting response. The N-terminal fragments of N/OFQ, (1–13) and (1–11), were antinociceptive with a potency lower than N/OFQ. Calculated ID50 values (nmol, i.t.) were 0.83 for N/OFQ, 2.5 for N/OFQ (1–13) and 4.75 for N/OFQ (1–11), respectively. The time-course effect revealed that the antinociceptive effects of these N-terminal fragments lasted longer than those of N/OFQ. Removal of amino acids down to N/OFQ (1–7) led to be less potent than N/OFQ and its fragments, (1–13) and (1–11). Antinociception induced by N/OFQ or N/OFQ (1–13) was reversed significantly by i.t. co-injection of [Nphe1]N/OFQ (1–13)NH2, a peptidergic antagonist for NOP receptors, whereas i.t. injection of the antagonist did not interfere with the action of N/OFQ (1–11) and (1–7). Pretreatment with the opioid receptor antagonist naloxone hydrochloride did not affect the antinociception induced by N/OFQ and its N-terminal fragments. These results suggest that N-terminal fragments of N/OFQ are active metabolites and may modulate the antinociceptive effect of N/OFQ in the spinal cord. The results also indicate that N/OFQ (1–13) still possess antinociceptive activity through NOP receptors. [Copyright &y& Elsevier]