Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Release of endogenous dynorphin opioids within the spinal cord after partial sciatic nerve ligation (pSNL) is known to contribute to the neuropathic pain processes. Using a phosphoselective antibody [kappa opioid receptor (KOR-P)] able to detect the serine 369 phosphorylated form of the KOR, we determined possible sites of dynorphin action within the spinal cord after pSNL. KOR-P immunoreactivity (IR) was markedly increased in the L4-L5 spinal dorsal horn of wild-type C57BL/6 mice (7-21 d) after lesion, but not in mice pretreated with the KOR antagonist nor-binaltorphimine (norBNI). In addition, knock-out mice lacking prodynorphin, KOR, or G-protein receptor kinase 3 (GRK3) did not show significant increases in KOR-P IR after pSNL. KOR-P IR was colocalized in both GABAergic neurons and GFAP-positive astrocytes in both ipsilateral and contralateral spinal dorsal horn. Consistent with sustained opioid release, KOR knock-out mice developed significantly increased tactile allodynia and thermal hyperalgesia in both the early (first week) and late (third week) interval after lesion. Similarly, mice pretreated with norBNI showed enhanced hyperalgesia and allodynia during the 3 weeks after pSNL. Because sustained activation of opioid receptors might induce tolerance, we measured the antinociceptive effect of the kappa agonist U50,488 using radiant heat applied to the ipsilateral hindpaw, and we found that agonist potency was significantly decreased 7 d after pSNL. In contrast, neither prodynorphin nor GRK3 knock-out mice showed U50,488 tolerance after pSNL. These findings suggest that pSNL induced a sustained release of endogenous prodynorphin-derived opioid peptides that activated an anti-nociceptive KOR system in mouse spinal cord. Thus, endogenous dynorphin had both pronociceptive and antinociceptive actions after nerve injury and induced GRK3-mediated opioid tolerance.
 ...
PMID:Neuropathic pain activates the endogenous kappa opioid system in mouse spinal cord and induces opioid receptor tolerance. 1514 Sep 29

Our previous study showed that electroacupuncture (EA) significantly attenuated inflammatory hyperalgesia. It has also been reported that EA analgesia in uninjured animals is mediated by mu and delta opioid receptors at 2-15 Hz and by kappa opioid receptor at 100 Hz. Because persistent pain changes neural response to external stimulation, we hypothesized that (1) the mechanisms of EA anti-hyperalgesia may be different under conditions of persistent pain and that (2) combining EA with a sub-effective dose of morphine could enhance EA anti-hyperalgesia. Hyperalgesia, decreased paw withdrawal latency (PWL) to a noxious thermal stimulus, was induced by subcutaneously injecting complete Freund's adjuvant (CFA) into the hind paws of rats. Selective antagonists against mu (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-ThrNH2, CTOP), delta (naltrinodole, NTI) and kappa (nor-binaltorphimine, BNI) opioid receptors were administered intrathecally 10 min before each of two EA treatments at acupoint Huantiao (GB30), one immediately post and the other 2 h post-CFA. Morphine was given (i.p.) 40 min before the second EA treatment. PWL was measured before and 2.5 and 5 h post-CFA. Both 10 and 100 Hz EA-produced anti-hyperalgesia were blocked spinally by mu- and delta- but not kappa-receptor antagonists. EA combined with a sub-threshold dose of morphine (2.5 mg/kg) enhanced anti-hyperalgesia additively (10 Hz EA) or synergistically (100 Hz EA) compared to that produced by each component alone. These results suggest selective involvement of mu and delta, but not kappa, receptors in EA-produced anti-hyperalgesia in rats. A combined EA and opioid drug protocol may provide an improved treatment strategy for inflammatory pain.
 ...
PMID:Involvement of opioid receptors in electroacupuncture-produced anti-hyperalgesia in rats with peripheral inflammation. 1531 82

This study assessed the effect of the kappa opioid receptor agonist U50,488 administered into the rat temporomandibular joint (TMJ) on nociceptive behavioral responses evoked by formalin injected into the same site. Groups consisted of females, stratified into proestrus and diestrus phases of the estrous cycle, and males. Intra-TMJ formalin induced significantly different dose-dependent responses among the three groups, with diestrus females showing greater responses than males or proestrus females; therefore, equi-nociceptive formalin doses were chosen to test the effects of U50,488. U50,488 significantly reduced formalin-induced nociceptive behavior in all groups, but the reduction was significantly greater in females, especially those in diestrus. Pre-injection of the selective kappa opioid receptor antagonist nor-binaltorphimine (nor-BNI) into the same site significantly attenuated the effect of U50488; U50,488 injection into the contralateral TMJ failed to reduce nociceptive behavior. These findings support a role for kappa opioid receptors local to the site of inflammation to modulate inflammatory pain. Furthermore, since plasma levels of ovarian hormones are low during diestrus, these findings are consistent with the suggestion that sex hormones may play an antagonistic role in these peripheral kappa-mediated effects.
 ...
PMID:Sexual dimorphism in the antinociception mediated by kappa opioid receptors in the rat temporomandibular joint. 1554 50

Classically, the cerebellum has been shown to be involved in motor and visual functions, although recent evidence point to new roles of this organ. Pain processing is one of the recently described functions of the cerebellum. According to the importance of the opioid system in nociception, a detailed characterization of the expression pattern of opioid peptides in the cerebellum is the first step towards understanding the precise involvement of this organ in pain management. By using two different approaches (reverse transcription/polymerase chain reaction and in situ hybridization), we have detected, for the first time, expression of the kappa opioid receptor (KOR) gene in the cerebellar cortex of the rat. Expression is found in the molecular and granular layers in all the lobules of the cerebellum. Approximately 34% of the cells present in the molecular layer express KOR mRNA. This work contributes to the deeper knowledge of the mechanisms that are involved in cerebellar function and may lead to a better understanding of the relationships between nociceptive activity and drug abuse potential.
 ...
PMID:Kappa opioid receptor is expressed in the rat cerebellar cortex. 1577 54

(+/-)-Pentazocine is widely used clinically to treat mild to moderate pain as a racemic compound. Although it is known that (-)-pentazocine acts as a kappa opioid receptor agonist to exhibit analgesic actions and (+)-pentazocine acts as a sigma receptor agonist without analgesic effects, their combined effect on memory has not been investigated in detail. In this study, the effect of (+)- and/or (-)-pentazocine on scopolamine-induced memory impairment in mice was investigated using spontaneous alternation performance in a Y-maze. (+)-Pentazocine (0.35 micromol/kg, s.c.) administered 30 min before behavioral testing significantly improved the impairment of spontaneous alternation induced by scopolamine. A higher dose of (-)-pentazocine (3.50 micromol/kg, s.c.) also reversed the scopolamine-induced impairment of alternation performance. Interestingly, the ameliorating effects of not only (+)-pentazocine, but also (-)-pentazocine were antagonized by a selective sigma receptor antagonist, N,N-dipropyl-2-[4-methoxy-3-(2-phenylenoxy)-phenyl]-ethylamine monohydrochloride (NE-100) (2.6 micromol/kg, i.p.). However, those effects were not antagonized by a selective kappa opioid receptor antagonist, nor-binaltorphimine (4.9 nmol/mouse, i.c.v.). Coadministration of (+)- and (-)-pentazocine (0.35 or 3.50 micromol/kg each) did not have any additive or antagonizing effects on the percent alternation. An antinociceptive effect was observed only with (-)-pentazocine (3.50 micromol/kg, s.c.), and was antagonized by nor-binaltorphimine (4.9 nmol/mouse, i.c.v.), but not by NE-100 (2.6 micromol/kg, i.p.). These results suggest that although the analgesic effect of pentazocine was mediated via kappa opioid receptors, the ameliorating effect on scopolamine-induced impairment of spontaneous alternation was mediated via sigma receptors, not via kappa opioid receptors.
 ...
PMID:Improvement of memory impairment by (+)- and (-)-pentazocine via sigma, but not kappa opioid receptors. 1612 82

The present available opioid receptor antagonists such as naloxone and naltrexone are not highly receptor selective. They may antagonize mu opioid receptors to affect the pain threshold of the patients with traumatic shock while they exert antishock effects. Therefore, they are not suitable for traumatic shock. It is very important to elucidate the subclass of opioid receptors that are closely associated with cardiovascular depression of traumatic shock and then choose their specific receptor antagonists to treat it. Traumatic shock was used in pentobarbital-anesthetized Wistar rats by right femur fracture plus hemorrhage (fixed hemorrhage at a rate of 20 mL/kg in experiment 1 or hemorrhage to 40 mmHg mean arterial blood pressure for 60 min in experiments 2 and 3), and the changes of myocardial and brain opioid receptors after traumatic shock, the antagonizing effects of mu, delta, and kappa opioid receptor antagonists on the cardiovascular depression of traumatic shock and the antishock effects of delta and kappa opioid receptor antagonists ICI174,864 and Nor-binaltorphimine (Nor-BNI) were observed. The results indicate that after traumatic shock, the number of myocardial and brain delta and kappa opioid receptors were significantly increased that were significantly associated with the decreased cardiovascular functions. mu Opioid receptors in the heart and brain did not change significantly. Intracerebral ventricular administration of ICI174,864 and Nor-BNI significantly antagonized the decreased cardiovascular function after traumatic shock and increased the survival rate of traumatic shock rats, but mu opioid receptor antagonist beta-funaltrexamine did not. Meanwhile, intravenous administration of delta and kappa opioid receptor antagonists ICI174,864 and Nor-BNI also significantly increased the mean arterial blood pressure, improved the hemodynamic parameters, and prolonged the survival rate of traumatic shock rats. These findings suggest that opioid receptors are involved in the cardiovascular depression of traumatic shock, and the subclass receptors are mainly delta and kappa opioid receptors. delta and kappa opioid receptor antagonists have good beneficial effects on traumatic shock.
 ...
PMID:Subclass opioid receptors associated with the cardiovascular depression after traumatic shock and the antishock effects of its specific receptor antagonists. 1624 34

Nociceptin/orphanin FQ (N/OFQ), a 17-amino-acid peptide, is an endogenous agonist whose receptor is similar in sequence to mu, delta and kappa opioid receptors. It has been reported that N/OFQ can block antinociceptive effects induced by opioid receptor agonists in the radiant heat tail-flick test and warm water tail-withdrawal test. The present study was designed to see the effect of N/OFQ on antinociception induced by opioid receptor agonists in the cold water tail-flick (CWT) test, which measures a different type of pain. In adult male Sprague-Dawley (S-D) rats given subcutaneous (s.c.) injections of saline or morphine (8 mg/kg), intracerebroventricular (i.c.v.) injection of N/OFQ (18 microg) 15 min later produced a significant reversal of morphine antinociception (P<0.01, ANOVA followed by Duncan's test), compared to the corresponding saline control group. Saline (t=+15 min, i.c.v.) had no effect on s.c. morphine antinociception (P>0.01), compared to the corresponding saline control group. When the kappa opioid receptor agonist spiradoline (80 mg/kg, s.c.) was used instead of morphine, similar results were observed. In another series of experiments, it was found that i.c.v. injection of N/OFQ (18 microg) reversed the antinociception induced by i.c.v. injection of the selective mu opioid agonist PL017 (2 microg), delta opioid agonist DPDPE (50 ng) and kappa opioid agonist dynorphin (21.5 microg), respectively. These results indicate that N/OFQ may be an endogenous anti-opioid peptide in the brain of rats in the CWT test.
 ...
PMID:Nociceptin/orphanin FQ blocks the antinociception induced by mu, kappa and delta opioid agonists on the cold water tail-flick test. 1717 91

The purpose of this study was to assess the possible antiallodynic effect of asimadoline ([N-methyl-N-[1S)-1-phenyl)-2-(13S))-3-hydroxypyrrolidine-1-yl)-ethyl]-2,2-diphenylacetamide HCl]) and ICI-20448 ([2-[3-(1-(3,4-Dichlorophenyl-N-methylacetamido)-2-pyrrolidinoethyl)-phenoxy]acetic acid HCl]), two peripheral selective kappa opioid receptor agonists, after subcutaneous, spinal and periaqueductal grey administration to neuropathic rats. Twelve days after spinal nerve ligation tactile allodynia was observed, along with an increase in kappa opioid receptor mRNA expression in dorsal root ganglion and dorsal horn spinal cord. A non-significant increase in periaqueductal grey was also seen. Subcutaneous (s.c.) administration of asimadoline and ICI-204448 (1-30 mg/kg) dose-dependently reduced tactile allodynia. This effect was partially blocked by s.c., but not intrathecal, naloxone. Moreover, intrathecal administration of asimadoline or ICI-204448 (1-30 mug) reduced tactile allodynia in a dose-dependent manner and this effect was completely blocked by intrathecal naloxone. Microinjection of both kappa opioid receptor agonists (3-30 mug) into periaqueductal grey also produced a naloxone-sensitive antiallodynic effect in rats. Our results indicate that systemic, intrathecal and periaqueductal grey administration of asimadoline and ICI-204448 reduces tactile allodynia. This effect may be a consequence of an increase in kappa opioid receptor mRNA expression in dorsal root ganglion, dorsal horn spinal cord and, to some extent, in periaqueductal grey. Finally, our data suggest that these drugs could be useful to treat neuropathic pain in human beings.
 ...
PMID:Subcutaneous, intrathecal and periaqueductal grey administration of asimadoline and ICI-204448 reduces tactile allodynia in the rat. 1764 11

Opioids remain the most effective analgesics despite their potential adverse effects such as tolerance and addiction. Mechanisms underlying these opiate-mediated processes remain the subject of much debate. Here we describe opioid-induced behaviors of Lmx1b conditional knockout mice (Lmx1bf/f/p), which lack central serotonergic neurons, and we report that opioid analgesia is differentially dependent on the central serotonergic system. Analgesia induced by a kappa opioid receptor agonist administered at the supraspinal level was abolished in Lmx1bf/f/p mice compared with their wild-type littermates. Furthermore, compared with their wild-type littermates Lmx1bf/f/p mice exhibited significantly reduced analgesic effects of mu and delta opioid receptor agonists at both spinal and supraspinal sites. In contrast to the attenuation in opioid analgesia, Lmx1bf/f/p mice developed tolerance to morphine analgesia and displayed normal morphine reward behavior as measured by conditioned place preference. Our results provide genetic evidence supporting the view that the central serotonergic system is a key component of supraspinal pain modulatory circuitry mediating opioid analgesia. Furthermore, our data suggest that the mechanisms of morphine tolerance and morphine reward are independent of the central serotonergic system.
 ...
PMID:Central serotonergic neurons are differentially required for opioid analgesia but not for morphine tolerance or morphine reward. 1772 36

The present study investigated the role of peripheral opioid receptors in mustard oil-induced nociceptive behavior and inflammation in the masseter muscles of lightly anesthetized rats. Experiments were carried out on male Sprague-Dawley rats weighing between 300 and 400 g. After initial anesthesia with sodium pentobarbital (40 mg/kg, i.p.), one femoral vein was cannulated and connected to an infusion pump for the intravenous infusion of sodium pentobarbital. The rate of infusion was adjusted to provide a constant level of anesthesia. Mustard oil (MO, 30 microl) was injected into the mid-region of the left masseter muscle via a 30-gauge needle. Intramuscularly-administered morphine significantly reduced shaking behavior but not MO-induced inflammation. Intramuscular pretreatment with naloxone, an opioid receptor antagonist, reversed antinociception produced by intramuscularly-administered morphine, while intracisternal administration of naloxone did not affect the antinociception of peripheral morphine. Pretreatment with d-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), a mu opioid receptor antagonist, but not naltrindole, a delta opioid receptor antagonist, nor norbinaltorphimine (nor-BNI), a kappa opioid receptor antagonist, reversed intramuscularly-administered morphine-induced antinociception. These results indicate that intramuscularly-administered morphine produces antinociception in craniofacial muscle nociception and that this intramuscularly-administered morphine-induced antinociception is mediated by a peripheral mu opioid receptor. Our observations further support the clinical approach of administering opioids in the periphery for the treatment of craniofacial muscle nociception.
Eur J Pain 2008 Apr
PMID:Intramuscular administration of morphine reduces mustard-oil-induced craniofacial-muscle pain behavior in lightly anesthetized rats. 1776 78


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>