Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of LPSw, a lipopolysaccharide from a water extract of wheat flour, on pain response was investigated using an acetic acid-induced writhing test in mice. LPSw inhibited writhing dose-dependently in the range of 10 ng-10 micrograms/mouse i.v. This effect reached its maximum 1.5-3 h after the LPSw inoculation and was detectable even after 8 h. The analgesic effect of LPSw was inhibited by i.v. injection of naloxone and also beta-endorphin was detected in serum and brain tissue following injection of LPSw. Preliminary clinical trials were done in which LPSw was administered percutaneously to relieve the pain of patients with herpes. The results showed that pain was relieved by this application. LPSw may be the best analgesic drug so far known, since it induces the endogenous mediator of analgesia, beta-endorphin.
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PMID:Homeostasis as regulated by activated macrophage. IV. Analgesic effect of LPSw, a lipopolysaccharide of wheat flour. 152 27

Activation of the immune system in response to either infection or lipopolysaccharide (LPS) produces neurophysiological, neuroendocrine and behavioral changes. Some of the physiological consequences of LPS are mediated by endogenous opioid peptides. The following studies were designed to characterize the effects of LPS in several behavioral paradigms, and to determine the role of opioids in mediating these effects. The effects of LPS on locomotor and self-care activity were assessed in the open field test. Rats were injected with either saline or a dose of LPS (25, 50, 100, or 1000 micrograms/kg). 4 h later, the animals were placed in an open field and the numbers of line crossings, rearings and grooming episodes were counted. LPS significantly suppressed the three open field behaviors in a dose-related manner. The effect of LPS on sensitivity to pain was determined using the hot-plate and tail-flick tests. Administration of LPS (200 micrograms/kg) increased pain sensitivity in the hot plate test 30 min after drug administration, but produced a significant analgesic response 4 h after drug administration in both tests. Further characterization of LPS-induced analgesia demonstrated that it began about 2 h after and disappeared 30 h after the administration of LPS. Administration of naltrexone completely blocked the analgesic effects of LPS 4 h after its administration, but had no effect on LPS-induced suppression of activity in the open field. The effect of LPS on body temperature was biphasic, producing hypothermia at 2 h and hyperthermia at 8-30 h after its administration. Naltrexone had no effect on the body temperature changes induced by LPS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Behavioral effects of lipopolysaccharide in rats: involvement of endogenous opioids. 792 30

Recent breakthroughs in cannabinoid research, including the identification of two cannabinoid receptors (CB receptors) and a family of endogenous ligands, the anandamides, may shed new light on the sequelae of pre- and perinatal exposure to cannabinoid receptor ligands and enable the experimental manipulation of the endogenous ligand in the developing organism. In the present study we examined the behavioural response to anandamide (ANA) in developing mice from day 13 into adulthood. We observed that depression of ambulation in an open field and the analgetic response to ANA are not fully developed until adulthood. In a separate set of experiments, we administered five daily injections of ANA (SC, 20 mg/kg) during the last trimester of pregnancy. No effects on birth weight, litter size, sex ratio and eye opening were detected after maternal ANA treatment. Further, no effects on open field performance of the offspring were observed until 4 weeks of age. However, from 40 days of age, a number of differences between the prenatal ANA and control offspring were detected. Thus, the offspring from ANA-treated dams showed impaired responsiveness to a challenge with ANA or delta 0-THC expressed as a lack of immobility in the ring test for catalepsy, hypothermia and analgesia. On the other hand, without challenge, they exhibited a spontaneous decrease in open field activity, catalepsy, hypothermia and a hypoalgetic tendency. These data suggest that exposure to excessive amounts of ANA during gestation alters the functioning of the ANA-CB receptor system. Further experiments investigating responsivity of the immune system suggest an increased inflammatory response to arachidonic acid, and enhanced hypothermic response to lipopolysaccharide in prenatally treated offspring. The results are discussed in relation to other manipulations of the maternal milieu, especially prenatal stress. It is concluded that alterations induced by prenatal exposure to ANA, cannabinoids and other psychotropic drugs or prenatal stress, share common features, but the data also suggest specific effects on the ANA-CB receptor system.
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PMID:Developmental aspects of anandamide: ontogeny of response and prenatal exposure. 877 60

We have previously demonstrated that illness-inducing agents (lipopolysaccharide (LPS)) and inflammatory agents (subcutaneous (s.c.) formalin) induce hyperalgesia by similar pathways. The present series of experiments compared the effects of medullary lesions on these phenomena. These experiments demonstrate that s.c. formalin-induced hyperalgesia, like illness-induced hyperalgesia, is dependent on the nucleus raphe magnus (NRM) but independent of the nucleus reticularis paragigantocellularis (NRPgc). However, these two forms of hyperalgesia differ with regards to their dependence on the nucleus tractus solitarius (NTS). Illness-induced hyperalgesia is abolished by unilateral (left) NTS lesions, whereas formalin-induced hyperalgesia remains unaffected by this procedure. These data provide further evidence that hyperalgesias induced by illness agents and by inflammatory agents are mediated by similar but not identical pathways. They also illustrate that neural structures have the capacity for opposed actions, in that both the NTS and NRM are documented to underlie hyperalgesia as well as analgesia. This capacity for opposed action may prove to be characteristic of structures involved in pain modulation.
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PMID:Comparison of the effects of nucleus tractus solitarius and ventral medial medulla lesions on illness-induced and subcutaneous formalin-induced hyperalgesias. 906 55

Gender-related differences in response to drugs of abuse, such as cocaine and morphine, have been reported both in humans and in experimental animals. Besides causing analgesia, morphine has recently been shown to exert strong immunosuppressive activity. However, no data on the influence of gender on the immunomodulatory effects of morphine or opioid peptides have been reported yet. The aim of this study was to test the influence of gender on the immunomodulatory ability of the endogenous opioid peptide [Met(5)]enkephalin (MENK) in mice. This was done by comparing the proliferative ability of splenic T- and B-lymphocytes 14 h after systemic (intraperitoneal; i.p.) administration of [Met(5)]enkephalin (2.5, 5 or 10 mg/kg body weight). The proliferative ability of T- and B-lymphocytes was assessed by testing their in vitro response to graded concentrations of the T- and B-cell mitogens, concanavalin-A (Con-A) and lipopolysaccharide (LPS), respectively. The results obtained showed that [Met(5)]enkephalin, at a dose of 2.5 mg/kg, enhanced the proliferative ability of T-lymphocytes in male mice, but not in female mice. Similarly, [Met(5)]enkephalin, at doses of 2.5 and 5 mg/kg, enhanced the proliferative ability of splenic B-lymphocytes in male mice, whereas in female mice a decrease was observed ([Met(5)]enkephalin 2.5 mg/kg, LPS 10 microg/ml). [Met(5)]enkephalin, at a dose of 10 mg/kg, did not affect the proliferative ability of either lymphocyte population, regardless of gender. The [Met(5)]enkephalin-induced stimulatory effect on both T- and B-lymphocyte proliferation was reversed by naloxone (10 mg/kg body weight), injected prior to [Met(5)]enkephalin, suggesting an involvement of opioid receptors. Thus, the data presented provide evidence for the gender-related response of murine splenic lymphocytes to immunomodulation by [Met(5)]enkephalin, administered in vivo. This finding may be relevant to the potential use of [Met(5)]enkephalin in adjuvant therapy for immunocompromised states, such as acquired immunodeficiency syndrome (AIDS) or malignancies.
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PMID:Gender-related differences in murine T- and B-lymphocyte proliferative ability in response to in vivo [Met(5)]enkephalin administration. 1074 78

Possible contributions of the hypothalamo-hypophyseal-adrenal axis to the development of adjuvant-induced arthritis and therapeutic actions of the prototypical kappa-opioid agonist PNU-50,488H (PNU-50) were studied in DA rats. Paw edema, nociception, histological and radiological joint damage, and tumor necrosis factor-alpha release by peritoneal macrophages were measured in adrenalectomized (ADX) and sham-operated (SHO) arthritic animals (drug-treated and untreated groups). Disease developed earlier in ADX rats (paw edema was first apparent 11 days postadjuvant compared with day 13 in SHO animals) and remained more severe in that group. Twice-daily PNU-50 treatment completely prevented the development of edema in the SHO group but was effective in the ADX animals only on day 18. PNU-50 substantially reduced the pooled severity index (combined quantitative edema, histological and radiological assessments) at day 18 in both SHO and ADX rats and to an equal extent. During disease development, the paws of SHO, but not ADX, rats became hyperalgesic; paradoxically, ADX animals were hyperalgesic during PNU-50 treatment, but the drug produced analgesia in SHO animals. Compared with cells harvested from healthy animals, macrophages from arthritic rats released about twice as much tumor necrosis factor-alpha after lipopolysaccharide stimulation. It was concluded that the hypothalamo-hypophyseal-adrenal axis influences the development of adjuvant arthritis and plays a partial role in the therapeutic action of the kappa-agonist PNU-50.
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PMID:The importance of the hypothalamo-hypophyseal-adrenal axis to the anti-inflammatory actions of the kappa-opioid agonist PNU-50,488H in rats with adjuvant arthritis. 1094 69

A decrease and subsequent increase in nociceptive threshold in the whole body are clinical symptoms frequently observed during the course of acute systemic infection. These biphasic changes in nociceptive reactivity are brought about by central signal substances induced by peripheral inflammatory messages. Systemic administration of lipopolysaccharide (LPS) or interleukin-1 beta (IL-1 beta), an experimental model of acute infection, may mimic the biphasic changes in nociception, hyperalgesia at small doses of LPS, and IL-1 beta and analgesia at larger doses. Our behavioral and electrophysiological studies have revealed that IL-1 beta in the brain induces hyperalgesia through the actions of prostaglandin E2 (PGE2) on EP3 receptors in the preoptic area and its neighboring basal forebrain, whereas the IL-1 beta-induced analgesia is produced by the actions of PGE2 on EP1 receptors in the ventromedial hypothalamus. An intravenous injection of LPS (10-100 micrograms/kg) produced hyperalgesia only during the period before fever develops and was abolished by microinjection of NS-398 (an inhibitor of cyclooxygenase 2) into the preoptic area, but not into the other areas in the hypothalamus. The hyperalgesia induced by the cytokines PGE2 and LPS may explain the systemic hyperalgesia clinically observed in the early phase of infectious diseases, which probably warns the organisms of infection before the full development of sickness symptoms. The switching of nociception from hyperalgesia to analgesia accompanied by sickness symptoms may reflect changes in the host's strategy for fighting microbial invasion as the disease progresses.
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PMID:Hypothalamic mechanisms of pain modulatory actions of cytokines and prostaglandin E2. 1126 35

Intraperitoneal (i.p.) injection of toxins, such as the bacterial endotoxin lipopolysaccharide (LPS), is associated with a well-characterized increase in sensitivity to painful stimuli (hyperalgesia) [Watkins LR, Maier SF, Goehler LE. Immune activation: the role of pro-inflammatory cytokines in inflammation, illness responses and pathological pain states. Pain 1995;63:289-302. [53]] and a longer-lasting reduction in opioid analgesia (anti-analgesia) when pain sensitivity returns to basal levels [Johnston IN, Westbrook RF. Acute and conditioned sickness reduces morphine analgesia. Behav Brain Res 2003;142:89-97]. Here we show that this inhibition of morphine analgesia 24 h after a single i.p. injection of LPS involves mechanisms that contribute to illness-induced hyperalgesia and the development of analgesic tolerance to morphine. Specifically, morphine analgesia was restored if LPS was preceded by systemic administration of a non-competitive NMDA receptor antagonist (MK-801), spinal infusion of a glial metabolic inhibitor (fluorocitrate), or intracerebroventricular microinjection of an opioid receptor antagonist (naloxone). Morphine analgesia was also restored if MK-801 was administered after LPS. These results demonstrate that LPS recruits similar, if not the same mechanisms that reduce morphine tolerance following opiate administration: namely, stimulation of opioid and NMDA receptors and recruitment of spinal glia.
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PMID:Inhibition of morphine analgesia by LPS: role of opioid and NMDA receptors and spinal glia. 1547 52

In the present study, we evaluated the effect of epidural analgesia on the alterations of gut barrier function elicited by endotoxin in rabbits. After the placement of an epidural catheter, 28 male rabbits were randomized into either 0.5% lidocaine (group E) or saline (group C) group. The solutions (0.4 mL/kg) were epidurally injected, followed by continuous infusion (0.1 mL . kg(-1) . h(-1)) throughout the study period. Under a continuous infusion of lipopolysaccharide (15 microg . kg(-1) . h(-1)), mean arterial blood pressure, intramucosal pH, and plasma thrombomodulin concentrations were measured. At 4 h, mean arterial blood pressure was lower (P < 0.05), intramucosal pH was higher (P < 0.01), and the progression of hemodilution more profound (P < 0.05) in group E versus group C, whereas plasma thrombomodulin levels were increased to a similar extent between the groups. With less wet-to-dry weight ratio of ileum, histopathological injury scores of gut mucosa were significantly less in group E versus group C (P < 0.01). In a separate series of experiments (n = 10 each group), mucosal permeability in group E was significantly less compared with group C (P < 0.05). Collectively, these studies showed that despite a significant decrease of perfusion pressure and arterial oxygen content, epidural analgesia minimized endotoxin-induced functional and structural injury of gut mucosa possibly through endothelium-independent mechanisms.
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PMID:Epidural analgesia prevents endotoxin-induced gut mucosal injury in rabbits. 1597 43

Bacterial endotoxin (lipopolysaccharide; LPS) evokes in rodents an adaptive sickness behavior. It also produces changes in stress hormones secretion and activity of brain serotonergic and noradrenergic systems that have been implicated in stress responses, fear, and anxiety. Acoustic startle reflex (ASR) is regarded as a protective behavioral response that is enhanced in threatening situations or following an aversive event, and it can be modulated by physiological and emotional state of an animal. Effects of intraperitoneal injections of LPS on ASR, prepulse inhibition (PPI), locomotor activity in open field, and blood plasma corticosterone concentration were studied in lines of mice that display high (HA line) or low (LA line) swim stress-induced analgesia and also differ in emotional behaviors, including the magnitude of ASR. In both lines LPS produced robust sickness behavior, as evidenced by a decrease in locomotion and body weight, and an increase in corticosterone concentration. However, in neither line LPS injections affected responses to acoustic stimuli as assessed by the ASR and PPI magnitudes. The findings suggest that in sickness behavior induced by LPS the protective responses to salient environmental stimuli are not impaired. The significance of this finding for the concept of sickness behavior is discussed.
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PMID:Lipopolysaccharide does not affect acoustic startle reflex in mice. 1765 39


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