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)

Central inflammation is an integral component and contributor of the pathology of many debilitating diseases and has been shown to produce spontaneous pain and hyperalgesia. Recently, administration of lipopolysaccharide (LPS) into the lateral ventricle of rats was shown to elicit both thermal hyperalgesia and tactile allodynia [K. Walker, A. Dray, M. Perkins, Hyperalgesia in rats following intracerebroventricular administration of endotoxin: effect of bradykinin B1 and B2 receptor antagonist treatment, Pain 65 (1996) 211-219]. In this study, we have replicated the LPS model with some adaptations and correlated the nociceptive behaviors with an increased expression of activated macrophages in the central nervous system. We also examined the effects of priming on LPS-induced decreases in thermal nociceptive thresholds and mechanical response thresholds following either central or peripheral administration. Intracerebroventricular (i.c.v.) administration of LPS (0.2 microgram/rat) did not alter either thermal (hot plate) or mechanical (von Frey filaments) thresholds compared to baseline values in the first few hours after injection. However, priming rats by pretreating with i.c.v. LPS (0.2 microgram) 24 h prior to testing with i.c.v. LPS (0.2 microgram) produced significant mechanical allodynia and thermal hyperalgesia. The mechanical allodynia had an onset of 80 min after injection and a duration of 5 h. A similar time course was observed for thermal hyperalgesia, although its expression was less pronounced. Immunohistochemical studies indicated an increased expression of activated macrophages in the brain parenchyma of primed rats but not in unprimed rats. Intraperitoneal (i.p., 2 mg/kg) administration of LPS had no significant effect on either thermal or mechanical thresholds in the first few hours after injection; however, priming rats via i.p. (0.2 mg/kg) or i.c.v. (0.2 microgram) LPS produced a reduction in both thermal nociceptive thresholds and mechanical response thresholds in rats given a subsequent i.p. injection of LPS. This study demonstrates that priming is an effective protocol for the induction of central inflammation and increases the duration of these behaviors after i.c. v. administration.
 ...
PMID:Priming enhances endotoxin-induced thermal hyperalgesia and mechanical allodynia in rats. 979 8

The antinociceptive potency of opioids is altered by stress. We have shown that repetitive exposure of rats to noxious heat produced stress-induced analgesia as detected by the tail-flick test, but decreased the potency of the opioid beta-endorphin in the periaqueductal gray region of the midbrain (PAG). In this study, we examined the effects of this same stressor on the antinociceptive actions of the alkaloid narcotic, morphine, following either i.p. or intracerebral administration. Regardless of the route of administration, a significant reduction in the narcotic's ability to produce antinociception during stress was observed. The stress-induced reduction in morphine's potency was reversed by the intrathecal administration of the cholecystokinin (CCK) receptor antagonist L-365,260 (0.1 ng per rat), suggesting that spinal CCK-dependent 'anti-analgesic' processes are involved. Since stress influences the potency of narcotics, it may be an important physiological component to be considered in the clinical management of pain. Moreover, CCK receptor antagonists may improve the reliability of narcotic therapy.
 ...
PMID:Stress reduces morphine's antinociceptive potency: dependence upon spinal cholecystokinin processes. 1019 56

Gonadal hormones may modulate analgesia responses induced by acute stress in humans and rats. To evaluate the effects of gonadal hormones in modifying neuropathic pain, we measured autotomy changes following sciatic nerve resection in ovariectomized rats and in the presence of estrogen replacement. Two groups of female rats were subjected to ovariectomy and sham surgery. Each group was then divided into two subgroups receiving subcutaneously sesame oil with or without estradiol benzoate (5 microg/day/rat). All rats then underwent sciatic nerve resection in one hindlimb. Degree of self-mutilation was measured daily for 8 weeks. Estradiol treatment resulted in significantly lower autotomy scores in ovariectomized rats (3.6 +/- 0.6 vs. 5.5 +/- 0.3, p < 0.01) and in sham-operated rats (3.4 +/- 0.7 vs. 5.1 +/- 0.4, p < 0.05). The results of this study indicate that estrogen can modify the autotomy behavior, an indicator of neuropathic pain, in rats after nerve injury.
 ...
PMID:Effects of estrogen on autotomy in normal and ovariectomized rats. 1045 69

The involvement of spinal serotonergic system in testosterone influence on formalin-induced pain was studied in male rats. Four weeks after castration, there was an analgesia in the late phase of formalin test that was reversed by intraperitoneal injection of testosterone enanthate (1 mg/kg) for 3 days. Flutamide (testosterone antagonist) produce analgesia in the late phase on intraperitoneal (10 mg/kg, IP) and intrathecal (60 microg/rat, IT) injections, but not on intracerebroventricular (60 microg/rat, ICV) administration. The antinociceptive effect of castration and IP flutamide (10 mg/kg) was abolished by pretreatment with 5,7-dihydroxytryptamine (5,7-DHT, 100 microg/rat, IT). IT-administered 5-HT (100 microg/rat) produced analgesia in the early and late phase of formalin test. Microdialysis sampling was used to characterize the extracellular concentration of 5-hydroxytryptamine (5-HT, serotonin) in the dorsal horn of the lumbar spinal cord. This technique demonstrated that levels of 5-HT were increased in 4-week castrated and IP flutamide (10 mg/kg) injected rats. The results may indicate that the analgesia produced by castration and flutamide administration is mediated through functional alteration in spinal cord serotonergic system.
 ...
PMID:Involvement of the spinal serotonergic system in analgesia produced by castration. 1054 57

Using distention of the small intestine as a visceral pain model, we investigated the effect of zaldaride maleate (ZAL), a selective inhibitor of calmodulin, on the depressor response. In pentobarbital-anesthetized rats, small intestine distention was induced by rapid application of intraluminal pressures of 40 cmH2O causing a reflex fall in arterial blood pressure. The depressor response to intestinal distention was abolished by intraperitoneal administration of capsaicin (5 mg/rat), which depletes neuropeptides such as substance P from the sensory neurons, on the mesenteric stalk and by neonatal pretreatment with capsaicin (50 mg/kg, s.c.). Morphine (20 mg/kg, s.c.) reduced the depressor response following intestinal distention. At doses of 3 mg/kg (i.v.) and higher, ZAL significantly reduced depressor response. The effect of morphine was reversed by naloxone (5 mg/kg, i.v.); the effect of ZAL was not affected. These results suggest that ZAL helps reduce the visceral pain induced by noxious stimulus and that the antinociceptive effect of ZAL is not mediated by opioid receptors.
 ...
PMID:Effect of zaldaride maleate, an antidiarrheal compound, on visceral pain reflex induced by small intestinal distention in anesthetized rats. 1066 44

Systemic administration of nicotinic receptor (nAChR) agonists is antinociceptive in models of acute pain whereas their intrathecal (i. t.) administration has been reported to be antinociceptive, nociceptive or without effect. It has been hypothesized that the action induced is dependent upon the subtype and location of the nAChR activated. In addition, there is considerable evidence that nAChR ligand-induced antinociception is mediated by other neurotransmitter systems via descending pathways from the brainstem to the spinal cord. The present study investigated the effects of i. t. and systemic administration of A-85380, a novel nAChR agonist, in the paw withdrawal model of acute thermal pain in the rat. Given i.t. , A-85380 (1 and 10 nmol/rat) decreased the latency to paw withdrawal by 2-4 s. This pronociception was accompanied by a spontaneous flinching behavior. Both of these effects were differentially blocked by i.t. pretreatment with the nAChR antagonists mecamylamine (10 nmol)>MLA (100 nmol)>DHbetaE (50% with 1000 nmol) but not by alpha-bungarotoxin (0% at 0.63 nmol). Given systemically, A-85380 (0.56 micromol/kg, i.p.) induced antinociception as indicated by an increased latency to paw withdrawal, an effect differentially altered by i.t. pretreatment with monoaminergic antagonists (100 nmol/rat). While mecamylamine and prazosin had no effect, scopolamine, methysergide and MDL 72222 partially antagonized and idazoxan completely antagonized A-85380-induced antinociception. Finally, as measured by in vivo microdialysis, levels of 5-HT, but not NE, in the i.t. space of the lumber region of the spinal cord were significantly increased following the systemic administration of A-85380. Together these data suggest that the nociceptive properties of spinally administered nAChR agents are not mediated by either an alpha(4)beta(2) or an alpha(7) subtype nAChR, whereas the antinociceptive properties of systemically-administered nAChR agents are mediated by descending noradrenergic, serotonergic and muscarinic inhibitory pathways.
 ...
PMID:Spinal mechanisms underlying A-85380-induced effects on acute thermal pain. 1092 80

Serotonergic systems are involved in the central regulation of nociceptive sensitivity. Fluoxetine, a selective inhibitor of the reuptake of serotonin (5-hydroxytryptamine, 5-HT), was administered orally (0.16, 0.32, 0.8 mg kg(-1) daily for 7 days), intraperitoneally (0.04, 0.08, 0.16 mg kg(-1) day(-1) for 7 days and a single dose of 0.32 mg kg(-1)) and intracerebroventricularly (10 microg/rat) to rats and nociceptive sensitivity was evaluated using the formalin test (50 microL of 2.5% formalin injected subcutaneously). The effect of fluoxetine was also studied in the presence of 5,7-dihydroxytryptamine creatinine sulfate (5,7-DHT) and after co-administration with morphine. Oral (0.8 mg kg(-1)), intraperitoneal (0.16 and 0.32 mg kg(-1)) and intracerebroventricular (10 microg/rat) fluoxetine induced antinociception in the late phase of the formalin test. Furthermore, intrathecal administration of 5-HT (100 microg/rat) induced an analgesic effect. The analgesic effect of fluoxetine (0.16 and 0.32 mg kg(-1), i.p.) and 5-HT (100 microg/rat, i.t.) was abolished by pre-treatment with 5,7-DHT (100 microg/rat, i.t.). In addition, the analgesic effect of 5-HT (100 microg/rat, i.t.) was decreased by pre-treatment with naloxone (2 mg kg(-1), i.p.). Morphine (5 mg kg(-1), i.p.) induced analgesia that was increased by fluoxetine (0.32 mg kg(-1), i.p.). These results suggest that fluoxetine has an antinociceptive effect in tonic inflammatory pain through functional alteration of the serotonergic system and also potentiates the analgesic effect of morphine.
 ...
PMID:Effect of chronic and acute administration of fluoxetine and its additive effect with morphine on the behavioural response in the formalin test in rats. 1127 19

Experiments were performed in carrageenin-treated rats to study, the antinociceptive and anti-inflammatory effects of paracetamol intravenously (i.v.) or intrathecally (i.t.) injected on rats submitted to a mechanical noxious stimulus. The influence of intrathecal tropisetron, a 5 hydroxytryptamine(3) (5-HT(3)) receptor antagonist, on the antinociceptive effects of paracetamol, was also studied. Paracetamol induced a significant antinociceptive effect after (100, 200 and 300 mg/kg) i.v. and (50, 100 and 200 microg/rat) i.t. injection, but no change occurred on edema volume. The effect of paracetamol was totally inhibited by tropisetron (10 microg/rat, i.t.). The foregoing results demonstrate that, in conditions of inflammatory pain, paracetamol exerts a central antinociceptive effect involving spinal 5-HT(3) receptors, without inducing any anti-inflammatory action. These data, give further arguments to consider paracetamol as a central analgesic drug which must be distinguished from non-steroidal anti-inflammatory drugs (NSAIDs), which justifies the usual combination of paracetamol in post-operative pain.
 ...
PMID:Paracetamol exerts a spinal, tropisetron-reversible, antinociceptive effect in an inflammatory pain model in rats. 1204 94

The NMDA receptor has been widely investigated in recent years as a target for the pharmacological management of seizures, pain and a variety of neurological disorders. Its role in normal central nervous system (CNS) activity and development, as well as in the development of CNS abnormalities and neurodegeneration has also been of interest. The NMDA receptor is one of three pharmacologically distinct subtypes of ionotropic receptor channels that are sensitive to the endogenous excitatory amino acid, L-glutamate. The ontogeny of the NMDA receptor, a multiple tetrameric and heteromeric channel complex with at least six known subunits, is controlled by three gene families and varies in developmental profile with species and regional brain area. NMDA receptors play a role in excitatory synaptic transmission, in the activity-dependent synaptic plasticity underlying learning and memory, and in pre- and postnatal CNS development, including brain cell differentiation, axonal growth and degeneration of unused neurons. The results of recent studies suggest that sustained alteration of NMDA receptor activation during critical periods of development may have deleterious effects on normal CNS development and function. Neonatal rats administered the NMDA receptor antagonists 2-amino-5-phosphonovalerate (AP5) and MK-801 during the first two weeks of life develop abnormal axonal arborization in the retinal connections to the superior colliculus, interfering with normal visual responses. Results from monkey studies suggest that chronic developmental exposure to high doses of a NMDA antagonist, remacemide, has pronounced and long-lasting effects on learning. Recent findings indicate that if NMDA receptors are blocked during a specific period in neonatal life (first two weeks postnatally in the rat), massive apoptotic neurodegeneration results, due not to excitotoxic overstimulation of neurons but to deprivation of stimulation. These observations require further laboratory evidence and support in order to establish their relevance to drug-induced human neurodevelopmental concerns. It is necessary to investigate the relevance of these findings in other animal species in addition to the rat, most notably, nonhuman primates, where neuronal cytoarchitecture and development are significantly different than the rodent but more like the human.
 ...
PMID:Ontogeny of the N-methyl-D-aspartate (NMDA) receptor system and susceptibility to neurotoxicity. 1207 5

Sex-related differences exist in nociception and gonadal steroids influence the analgesic response in animals and humans. As we have shown previously, estrogen could modify autotomy in female rats using the sciatic nerve transection model. To further characterize the relationship between gonadal steroid and nociception, the role of testosterone on autotomy in sciatic nerve sectioned rats was investigated. Twenty male rats were subjected to orchiectomy (ORX). Then ten rats received subcutaneous sesame oil and the other ten were treated with testosterone propionate in sesame oil (TP; 500 microg/day/rat). All the rats underwent sciatic nerve resection in left hind limb. Degree of self-mutilation was measured daily for 8 weeks. TP reinstatement resulted in significantly lower autotomy scores in orchiectomized rats. The results demonstrated that testosterone could modify the autotomy behavior, an indicator of neuropathic pain, in rats after nerve injury.
 ...
PMID:Influence of testosterone on autotomy in castrated male rats. 1215 Jan 98


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