norbinaltorphimine and Inflammation

Antinociception induced by the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) is linked to opioid receptors. We studied the subtype of receptors to which CPA action is related, as well as a possible enhancement of antinociception when CPA is coadministered with opioid receptor agonists. Spinal cord neuronal nociceptive responses of male Wistar rats with inflammation were recorded using the single motor unit technique. CPA antinociception was challenged with naloxone or norbinaltorphimine. The antinociceptive activity of fentanyl and U-50488H was studied alone and combined with CPA. Reversal of CPA antinociception was observed with norbinaltorphimine (82.9±13% of control) but not with low doses of naloxone (27±8% of control), indicating an involvement of κ-opioid but not µ-opioid receptors. Low doses of CPA did not modify fentanyl antinociception. However, a significant enhancement of the duration of antinociception was seen when U-50488H was coadministered with CPA. We conclude that antinociception mediated by CPA in the spinal cord is associated with activation of κ-opioid but not µ-opioid receptors in inflammation. In addition, coadministration of CPA and κ-opioid receptor agonists is followed by significantly longer antinociception, opening new perspectives in the treatment of chronic inflammatory pain.

Topics: Adenosine; Animals; Carrageenan; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Electric Stimulation; Fentanyl; Inflammation; Male; Naloxone; Naltrexone; Narcotic Antagonists; Pain; Pain Measurement; Rats; Rats, Wistar; Receptors, Opioid, kappa; Reflex; Spinal Cord

In an attempt to decrease central side effects associated with the use of opioids, some strategies have been developed by targeting peripheral opioid receptors. In this context, kappa receptors are of major interest, since, in contrast to other opioid receptors, their activation is not associated with potent peripheral side effects. We have recently demonstrated that local activation of kappa opioid receptors significantly decreases formalin-induced temporomandibular joint nociception; however, whether it also decreases temporomandibular joint inflammation is not known. To address this issue, we evaluated if a specific kappa opioid receptor agonist, U50,488 (trans-(1S,2S)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide hydrochloride hydrate), administered into the temporomandibular joint decreases formalin-induced plasma extravasation and neutrophil migration. Ipsilateral, but not contralateral, administration of U50,488 into the temporomandibular joint blocked formalin-induced plasma extravasation and neutrophil migration in a dose-dependent manner. This anti-inflammatory effect was reversed by the ipsilateral, but not contralateral, administration of the kappa opioid receptor antagonist nor-BNI (nor-binaltorphimine dihydrochloride). This study demonstrates that local activation of kappa opioid receptors decreases two important parameters of temporomandibular joint inflammation, that is, plasma extravasation and neutrophil migration, in a dose-dependent and antagonist-reversible manner. This anti-inflammatory effect taken together with the potent antinociceptive effect, suggests that drugs targeting peripheral kappa opioid receptors are promising for the treatment of inflammatory temporomandibular joint pain and probably, other articular pain conditions with an inflammatory basis.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Movement; Dose-Response Relationship, Drug; Formaldehyde; Inflammation; Male; Naltrexone; Neutrophil Infiltration; Neutrophils; Rats; Rats, Wistar; Receptors, Opioid, kappa; Temporomandibular Joint

Although studies demonstrate that electroacupuncture (EA) alleviates the sensory dimension of pain, they have not addressed EA's effect on the affective dimension. An inflammatory pain rat model, produced by a complete Freund adjuvant (CFA) injection into the hind paw, was combined with a conditioned place avoidance test to determine EA's effects and its underpinning mechanism on the affective dimension of pain. CFA-injected rats showed place aversion, i.e. the affective dimension of pain, by spending less time in a pain-paired compartment after conditioning than before, while saline-injected rats did not. CFA rats given EA treatment at GB30 before a post-conditioning test showed no aversion to the pain-paired compartment, indicating that EA inhibited the affective response. Intra-rostral anterior cingulate cortex (rACC) administration of a κ-, but not μ-opioid receptor antagonist, blocked EA action. These data demonstrate that EA activates opioid receptors in the rACC to inhibit the affective dimension of pain.

Topics: Affect; Animals; Avoidance Learning; Conditioning, Classical; Disease Models, Animal; Electroacupuncture; Freund's Adjuvant; Gyrus Cinguli; Hyperalgesia; Inflammation; Male; Naltrexone; Pain Management; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa; Receptors, Opioid, mu; Somatostatin

This investigation determined whether the activation of the kappa opioid receptor (KOR) in the spinal cord produces estrogen-dependent, sex-specific modulation of acute and inflammation-induced persistent nociception. We demonstrate for the first time that KOR antinociception and gene expression are enhanced by exogenous or endogenous estrogen in the female. The lack of KOR antinociception and KOR gene expression are not altered by the hormonal status (testosterone or estrogen) in males. Cannulae were implanted intrathecally in male, gonadectomized male (GDX), intact and ovariectomized female (OVX) Sprague-Dawley rats. Estradiol was injected subcutaneously, 48h before testing (GDX+E and OVX+E). Intrathecal injection of U50,488H, a selective KOR agonist, dose dependently increased heat-evoked tail flick latencies (TFLs) in proestrous and OVX+E groups, but not in male, GDX, GDX+E, OVX, and diestrous groups. Further, estrogen dose-dependently enhanced the effect of U50,488H in OVX rats. KOR selective antagonist, nor-binaltorphimine (Nor-BNI), blocked the antinociceptive effect of U50,488H. U50,488H reversed the carrageenan-induced thermal hyperalgesia in OVX+E rats, but not in male or OVX rats. However, U50,488H treatment did not alter mechanical thresholds in any group, with or without inflammation. KOR gene expression was enhanced in proestrous and OVX+E groups as compared to any other group. We conclude that selective activation of KOR in the spinal cord produces sex-specific, stimulus- and estrogen-dependent attenuation of acute and inflammatory pain in the rat via estrogen-induced upregulation of the KOR gene expression in the spinal cord. These findings may further implicate estrogen dependence of KOR effects in learning, epilepsy, stress response, addiction etc.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesia; Analgesics, Non-Narcotic; Analysis of Variance; Animals; Area Under Curve; Dose-Response Relationship, Drug; Estradiol; Estrous Cycle; Female; Inflammation; Injections, Spinal; Lumbosacral Region; Male; Naltrexone; Orchiectomy; Ovariectomy; Pain; Pain Measurement; Pain Threshold; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa; Reverse Transcriptase Polymerase Chain Reaction; Sex Characteristics; Spinal Cord; Testosterone

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.

Topics: Analgesics; Anesthesia, General; Animals; Inflammation; Injections; Injections, Intramuscular; Male; Masseter Muscle; Morphine; Mustard Plant; Naloxone; Naltrexone; Narcotic Antagonists; Nociceptors; Pain; Plant Oils; Psychomotor Performance; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Single-Blind Method; Somatostatin

It has been shown that inflammation of rat paws elicits accumulation of opioid peptide beta-endorphin-containing immune cells in the inflamed subcutaneous tissue, contributing to immunocyte-produced pain suppression. However, the possible mechanisms involved in the pharmacological application of beta-endorphin in rat paw inflammation have not been investigated. The present study was set up to explore the effects of intraplantar injection of beta-endorphin on Concanavalin A-induced paw edema in two inbred rat strains, Albino Oxford (AO) and Dark Agouti (DA). Both high dose-induced suppression and low dose-induced potentiation of edema development in AO and DA rats, respectively, were blocked with antagonists specific for delta (naltrindole) and kappa (nor-binaltorphimine) opioid receptors. beta-endorphin in vitro decreased phagocytosis and increased nitric oxide (NO) production in air pouch granulocytes obtained from AO rats. However, in cells from DA rat strain beta-endorphin modulated both phagocytosis and NO production in a concentration-dependent manner. It could be concluded that the strain-dependent opposing effects of beta-endorphin on paw inflammation are mediated through delta and kappa opioid receptors and probably involve changes in the production of reactive oxygen species by inflammatory cells. Our results point to the importance of genotype for pharmacological manipulations and the development of inflammation.

Topics: Animals; beta-Endorphin; Concanavalin A; Dose-Response Relationship, Drug; Edema; Female; Granulocytes; Hindlimb; Inflammation; Male; Naltrexone; Narcotic Antagonists; Neurotransmitter Agents; Nitric Oxide; Phagocytosis; Rats; Rats, Inbred Strains; Receptors, Opioid, delta; Receptors, Opioid, kappa; Species Specificity

Recent clinical studies have demonstrated that when morphine is used to control pain in cancer patients, psychological dependence is not a major concern. The present study was undertaken to ascertain the modulation of psychological dependence on morphine under a chronic pain-like state in rats. The prototypical mu-opioid receptor agonist morphine (8 mg/kg, i.p.) induced a dose-dependent place preference. In the present study, we found that an inflammatory pain-like state following formalin injection significantly suppressed the morphine-induced rewarding effect. This effect was almost reversed by s.c. pretreatment with the kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI, 5 mg/kg). Furthermore, the morphine-induced increase in dopamine (DA) turnover in the limbic forebrain was significantly inhibited by treatment with formalin. This inhibition was also suppressed by pretreatment with nor-BNI. In addition, in vivo microdialysis studies clearly showed that the morphine-induced increase in the extracellular levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in the nucleus accumbens (N.Acc.) was significantly decreased in rats that had been pretreated with formalin. This effect was in turn reversed by the microinjection of a specific dynorphin A antibody into the N.Acc. These findings suggest that the inflammatory pain-like state induced by formalin injection may have caused a sustained activation of the kappa-opioidergic system within the N.Acc., resulting in suppression of the morphine-induced rewarding effect in rats. The present study provides further evidence of the clinical usefulness of morphine in patients suffering from severe pain.

Topics: Animals; Brain Chemistry; Conditioning, Operant; Dopamine; Dynorphins; Edema; Foot; Formaldehyde; Inflammation; Limbic System; Male; Microdialysis; Microinjections; Morphine; Naltrexone; Narcotic Antagonists; Narcotics; Pain; Pain Measurement; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa; Reward

The present study was conducted on rats with inflammation induced by subcutaneous injection of carrageenan into the left hindpaw. Intrathecal administration of oxytocin produced dose-dependent increases in the hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation in rats with inflammation. The antinociceptive effect of oxytocin was blocked by intrathecal administration of atosiban, a selective oxytocin antagonist, indicating that oxytocin receptor mediates oxytocin-induced antinociception in the spinal cord. The oxytocin-induced antinociceptive effect was attenuated by intrathecal administration of the opioid antagonist naloxone, suggesting an involvement of the endogenous opioid system in oxytocin-induced antinociception in the spinal cord of rats with inflammation. Furthermore, the antinociceptive effect of oxytocin was attenuated by intrathecal injections of the mu-receptor antagonist beta-funaltrexamine and the kappa-receptor antagonist nor-binaltorphimine, but not by the delta-receptor antagonist naltrindole, illustrating that mu- and kappa-receptors, but not delta-receptor, are involved in oxytocin-induced antinociception in the spinal cord of rats with inflammation. Moreover, intrathecal administration of atosiban alone induced a hyperalgesia in rats with inflammation, indicating that endogenous oxytocin is involved in the transmission and regulation of nociceptive information in the spinal cord of rats with inflammation. The present study showed that both exogenous and endogenous oxytocin displayed antinociception in the spinal cord in rats with inflammation, and mu- and kappa-receptors were involved in oxytocin-induced antinociception.

Topics: Analgesics; Animals; Carrageenan; Hot Temperature; Inflammation; Injections, Spinal; Male; Naloxone; Naltrexone; Narcotic Antagonists; Oxytocin; Pain; Pain Measurement; Physical Stimulation; Rats; Rats, Wistar; Spinal Cord; Vasotocin

The effect of intraplantarly (i.pl.)-injected methionine-enkephalin (ME) on Concanavalin A (Con A)-induced paw edema in Dark Agouti (DA) and Albino Oxford (AO) rats was investigated. ME suppressed edema in DA rats, which was antagonized with naloxone (non-selective opioid receptor antagonist) and naltrindole (delta opioid receptors antagonist). Potentiating effect of ME in AO rats was blocked by naloxone, nor-binaltorphimine (kappa opioid receptors antagonist) and beta-funaltrexamine (mu opioid receptors antagonist). Dexamethasone suppressed edema in both rat strains. These findings suggest that strain-dependent differences in the effects of ME on inflammation in DA and AO rats could be related to diversity in opioid receptors expression in these strains.

Topics: Animals; Dexamethasone; Dose-Response Relationship, Drug; Edema; Enkephalin, Methionine; Glucocorticoids; Inflammation; Kinetics; Male; Naloxone; Naltrexone; Narcotic Antagonists; Rats; Species Specificity; Time Factors

This study investigates two new kappa-agonist tetrapeptides, FE 200665 and FE 200666, with high peripheral selectivity as a result of poor central nervous system penetration.. Four days after administration of Freund adjuvant into the hind paw of male Wistar rats, antinociceptive effects of intraplantar and subcutaneous injection of FE 200665 and FE 200666 were measured by paw pressure algesiometry and compared with the kappa-agonist U-69,593. Peripheral and kappa-receptor selectivity was assessed by the antagonists naloxone methiodide (NLXM) and nor-binaltorphimine, respectively. Antiinflammatory effects were evaluated by paw volume plethysmometry and histologic score.. Similar to intraplantar U-69,593, intraplantar FE 200665 (3-100 microg) and FE 200666 (1-30 microg) resulted in significant and dose-related increases of paw pressure thresholds. Higher doses of FE 200665 (0.2-20 mg) and FE 200666 (0.06-6 mg) were required by subcutaneous route to produce similar antinociceptive responses, supporting a peripheral site of action. nor-Binaltorphimine dose-dependently antagonized this effect, implying kappa-opioid selectivity. Analgesic effects of subcutaneous FE 200665 and FE 200666 were abolished by intraplantar nor-binaltorphimine, and both subcutaneous and intraplantar effects were dose-dependently antagonized by subcutaneous NLXM, further demonstrating a peripheral site of action. One to 6 days after Freund adjuvant inoculation, single and repeated intraplantar injections of FE 200665, FE 200666, and U-69,593 significantly reduced paw volume and histologic scores. Both changes were reversed by intraplantar nor-binaltorphimine and subcutaneous NLXM.. FE 200665 is a peripherally selective kappa-agonist with potent analgesic and antiinflammatory properties that may lead to improved analgesic-antiinflammatory therapy compared with centrally acting opioids or standard nonsteroidal antiinflammatory drugs.

Topics: Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzeneacetamides; Dose-Response Relationship, Drug; Inflammation; Injections, Spinal; Male; Naloxone; Naltrexone; Narcotic Antagonists; Opioid Peptides; Pain Threshold; Pyrrolidines; Rats; Rats, Wistar; Receptors, Opioid, kappa

We previously reported that the morphine-induced place preference was attenuated under inflammation produced by the unilateral injection of 2.5 % formalin (50 microl) into the hind paw of rats. In the present study, to elucidate the mechanism of this attenuation, the effects of pretreatment with delta- and kappa-opioid receptor antagonists, naltrindole (NTI) and nor-binaltorphimine (nor-BNI), on the development of the morphine-induced place preference under inflammation were examined in rats. Nor-BNI, but not NTI, eliminated the suppression of the morphine-induced place preference in inflamed groups. These results suggest that endogenous kappa-opioid systems may be activated in the presence of chronic inflammatory nociception; as a result, the development of morphine's rewarding effect may be suppressed under inflammation.

Topics: Animals; Chronic Disease; Conditioning, Psychological; Formaldehyde; Hindlimb; Inflammation; Male; Morphine; Naltrexone; Pain; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta; Receptors, Opioid, kappa; Reward; Time Factors

This study performed in freely moving rats evaluated the ability of specific opioid receptor antagonists to reverse the inhibitory effects of morphine on carrageenin-induced c-Fos expression in the spinal cord. Our study focused on the superficial dorsal horn (laminae I-II), which is the main termination site of nociceptive primary afferent fibers and is rich in opioid receptors. In order to replicate clinical routes of administration, all agents were administered intravenously (i.v.). As previously demonstrated, pre-administered i.v. morphine (3 mg/kg) produced a marked decrease (58+/-5%) in the number of Fos-LI neurones measured at 2 h after intraplantar (i.pl.) carrageenin (6 mg/150 microl) and yet was without influence on peripheral oedema. This decrease in c-Fos expression was completely blocked by combined administration of morphine with the mu-opioid receptor antagonist, [D-Phe-Cys-Tyr-D-Orn-Thr-Pen-Thr-NH2] (CTOP-1+1 mg/kg). Naltrindole (NTI-1+1 mg/kg), a delta-opioid receptor antagonist partially blocked the effects of systemic morphine, so that the inhibitory effects of morphine after NTI injection are now 40+/-4%. However, this effect of NTI was weak since the depressive effects of morphine were still highly significant (p<0.001). In contrast, nor-binaltorphimine (nor-BNI-1+1 mg/kg), a kappa-opioid receptor antagonist, had no significant effect on the effects of morphine. These results indicate the major contribution of mu-opioid receptors to the antinociceptive effects of systemic morphine at the level of the superficial dorsal horn. The observed effect of NTI is not necessarily related to a direct action of morphine on delta-opioid receptors and some possible actions of this antagonist are discussed.

Topics: Analgesics, Opioid; Animals; Carrageenan; Hindlimb; Inflammation; Injections, Intravenous; Male; Morphine; Naltrexone; Narcotic Antagonists; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Somatostatin; Spinal Cord

In an attempt to study the anti-inflammatory and the antinociceptive effects of a kappa1-opioid receptor agonist (U-69,593: trans-3,4-dichloro-N-methyl-N-[7-(1-pyrrolidinyl)cycloexil]benzene acetamide methanesulfonate), we used a combination of the measurement of peripheral oedema (with a calliper) and Fos immunodetection in the carrageenin model of inflammation. The intraplantar injection of carrageenin-induced the development of a peripheral oedema, associated with an increase in Fos-like immunoreactivity at the level of the dorsal horn of the spinal cord. U-69,593 administered intravenously (i.v.) 10 min before carrageenin administration over the dose range 0.75, 1.5 and 3 mg/kg, reduced both paw and ankle oedema in a non dose-dependent manner. The maximal decrease was observed at the highest dose and did not exceed 21% and 20% for the paw and the ankle respectively. These effects were kappa-opioid receptor specific since the anti-inflammatory effect of 1.5 mg/kg i.v. of U-69,593 was antagonised by a specific kappa-opioid receptor antagonist nor-binaltorphimine. Pre-treatment with U-69,593 strongly decreased the number of Fos-like Immunoreactive neurones of the spinal cord in a dose-dependent, antagonist reversible manner; maximal effect was 65%. The disparate results between the anti-inflammatory effects and the depressive effects on Fos expression suggest that anti-inflammatory effects of kappa-opioid receptor agonist are of minor importance for the antinociceptive effects of this compound.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Benzeneacetamides; Carrageenan; Dose-Response Relationship, Drug; Drug Interactions; Edema; Immunochemistry; Inflammation; Male; Naltrexone; Narcotic Antagonists; Photomicrography; Proto-Oncogene Proteins c-fos; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa; Spinal Cord

This electrophysiological study uses the mixed peptidase inhibitor kelatorphan and the selective kappa-antagonist nor-binaltorphimine (nor-BNI) to investigate whether there is altered modulation of spinal nociceptive transmission by endogenous opioids 3 h after injection of carrageenan into the ipsilateral paw. Intrathecal kelatorphan (5-250 micrograms) inhibited the C-fibre evoked response of dorsal horn neurones in both normal and carrageenan animals, with no difference in this inhibitory effect found between the 2 groups of animals. In both groups of animals, this inhibition reached a plateau at 50%. Thus there was no change in the effects exerted by the spinal enkephalins at this point in the inflammatory state. Nor-BNI (10 and 100 micrograms) produced a bidirectional change in the C-fibre evoked response of dorsal horn neurones in both normal and carrageenan animals, facilitating the evoked response of some neurones whilst inhibiting others. The magnitude of the change in the neuronal response induced by nor-BNI in carrageenan animals was significantly greater than that seen in normal animals, suggesting a greater release of spinal dynorphin in the inflammatory state. Dorsal horn neurones showed a bidirectional change in response as carrageenan-induced inflammation developed, although the direction of this change did not correlate with the subsequent direction of effect of nor-BNI. There was, however, a significant correlation between the magnitude of the change in the C-fibre evoked response after the injection of carrageenan and the magnitude of change produced in the same cells by nor-BNI.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analgesics; Animals; Carrageenan; Dipeptides; Dynorphins; Electrophysiology; Endorphins; Inflammation; Injections, Spinal; Male; Microelectrodes; Naltrexone; Nerve Fibers; Neurons; Nociceptors; Rats; Rats, Sprague-Dawley; Spinal Cord; Synaptic Transmission

The role of the endogenous kappa opioid system in the control of neuronal activity has been studied in the spinal cord of normal rats and in rats with Freund's adjuvant induced unilateral inflammation of the ankle under barbiturate anaesthesia. During recordings from neurons with ankle input the kappa receptor agonist U50,488H and/or the kappa antagonist nor-binaltorphamine were administered ionophoretically using multibarrel electrodes. In most neurons tested U50,488H reduced the responses evoked by pressure applied across the ankle whereas smaller proportions of neurons showed increased activity or were not affected. The kappa opioid antagonist nor-binaltorphamine affected more neurons in rats with inflammation than in control rats. Ongoing activity was increased in 7 of 19 (37%) neurons in control rats, in 16 of 24 (67%) neurons in the acute phase of inflammation (2 days post inoculation) and in 15 of 23 (65%) neurons in the chronic phase of inflammation (16-20 days post inoculation). During application of nor-binaltorphamine in control rats, the responses to pressure were increased in 9 cells (36%), reduced in 7 cells (28%) and unaffected in 9 cells (36%). In the acute phase of inflammation significantly more neurons (11 of 15, 73%) showed enhanced responses to pressure during ionophoresis of nor-binaltorphamine but not in the chronic phase. These results show that spinal cord neurons with ankle input are influenced by the endogenous kappa opioid system particularly under inflammatory conditions. The upregulation of this system under inflammatory conditions may serve to counteract inflammation-induced hyperexcitability.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; Arthritis, Experimental; Freund's Adjuvant; Inflammation; Joints; Male; Naltrexone; Neurons; Pyrrolidines; Rats; Rats, Wistar; Receptors, Opioid, kappa; Reference Values; Spinal Cord; Stress, Mechanical