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

Cold water swim (CWS) analgesia in the rat is mediated by the hypothalamo-pituitary-adrenocortical (HPA) axis. An age-dependent increase of CWS-induced analgesia was observed in male Sprague-Dawley young (4 months), adult (15 months) and old (26 months) rats. Acetyl-L-Carnitine (ALCAR) chronically administered (75 mg/kg/daily in drinking water for 8 months) to old rats was able to maintain the stress-dependent response at the same levels as in adult rats. This effect may be explained by ALCAR capability of retarding the age-dependent loss of glucocorticoid receptors in the hippocampus, thus maintaining the glucocorticoid competence of this structure which exerts a negative feedback control over the HPA axis activity.
 ...
PMID:Effect of long-term acetyl-L-carnitine on stress-induced analgesia in the aging rat. 782 64

Distal symmetrical peripheral neuropathy is a common adverse experience in persons with HIV infection. This condition, which presents as a pain, numbness. burning and/or dysaethesia initially in the feet, is often multi-factorial in its origin. Nucleoside analogue reverse transcriptase inhibitors represent an important contributor to peripheral neuropathy. Specifically, around 10% of patients receiving stavudine or zalcitabine and 1 to 2% of didanosine recipients may have to discontinue therapy with these agents due to neuropathy. Prompt withdrawal of these therapies enables gradual resolution of signs and symptoms in most patients, although a period of symptom intensification may occur shortly after withdrawal. Risk factors for developing peripheral neuropathy during nucleoside analogue therapy include low CD4+ cell count (<100 cells/mm3), a prior history of an AIDS defining illness or neoplasm, a history of peripheral neuropathy, use of other neurotoxic agents including high alcohol (ethanol) consumption and nutritional deficiencies such as low serum hydroxocobalamin levels. Thus, patients at increased risk of peripheral neuropathy should potentially avoid the use of the neurotoxic nucleoside analogues or be more carefully monitored during therapy. Management of this problem includes patient education. prompt withdrawal of the likely causative agent (giving consideration not to leave the patient on a sub-optimal therapy regimen) and simple analgesia. with augmentation with tricyclic antidepressants or anticonvulsant agents when pain is severe. New agents that may assist in managing this condition include levacecarnine (acetyl-L-carnitine) and nerve growth factors such as recombinant human nerve growth factor.
 ...
PMID:Peripheral neuropathy with nucleoside antiretrovirals: risk factors, incidence and management. 988 91

The cellular events involved in acetyl-L-carnitine (ALCAR) analgesia were investigated in the mouse hot plate test. I.c.v. pretreatment with aODNs against the alpha subunit of G(q) and G(11) proteins prevented the analgesia induced by ALCAR (100 mg kg(-1) s.c. twice daily for 7 days). Administration of the phospholipase C (PLC) inhibitors U-73122 and neomycin, as well as the injection of an aODN complementary to the sequence of PLCbeta(1), antagonized the increase of the pain threshold induced by ALCAR. Pretreatment with U-73343, an analogue of U-73112 inactive on PLC, did not modify ALCAR analgesic effect. In mice undergoing treatment with LiCl, which impairs phosphatidylinositol synthesis, or pretreatment with TMB-8, a blocker of Ca(++) release from intracellular stores, the antinociception induced by ALCAR was dose-dependently antagonized. I.c.v. treatment with heparin, an IP(3) receptor antagonist, prevented the increase of pain threshold induced by the investigated compound, analgesia that was restored by co-administration of D-myo-inositol. On the other hand, i.c.v. pretreatment with the selective protein kinase C (PKC) inhibitors calphostin C and cheleritryne, resulted in a dose-dependent potentiation of ALCAR antinociception. The administration of PKC activators, such as PMA and PDBu, dose-dependently prevented the ALCAR-induced increase of pain threshold. Neither aODNs nor pharmacological treatments produced any behavioral impairment of mice as revealed by the rota-rod and hole board tests. These results indicate that central ALCAR analgesia in mice requires the activation of the PLC-IP(3) pathway. By contrast, the simultaneous activation of PKC may represent a pathway of negative modulation of ALCAR antinociception.
 ...
PMID:Acetyl-L-carnitine requires phospholipase C-IP3 pathway activation to induce antinociception. 1522 7

Peripheral neurotoxicity is a major complication associated with the use of chemotherapeutic agents such as platinum compounds, taxanes and vinca alkaloids. The neurotoxicity of chemotherapy depends not only on the anticancer agent(s) used, the cumulative dose and the delivery method, but also on the capacity of the nerve to cope with the nerve-damaging process. The sensory and motor symptoms and signs of neurotoxicity are disabling, and have a significant impact on the quality of life of cancer patients. Moreover, the risk of cumulative toxicity may limit the use of highly effective chemotherapeutic agents. Therefore, prophylaxis and treatment of peripheral neurotoxicity secondary to chemotherapy are major clinical issues. Acetyl-L-carnitine (ALC), the acetyl ester of L-carnitine, plays an essential role in intermediary metabolism. Some of the properties exhibited by ALC include neuroprotective and neurotrophic actions, antioxidant activity, positive actions on mitochondrial metabolism, and stabilisation of intracellular membranes. ALC has demonstrated efficacy and high tolerability in the treatment of neuropathies of various aetiologies, including chemotherapy-induced peripheral neuropathy (CIPN). In several experimental settings, the prophylactic administration of ALC prevented the occurrence of peripheral neurotoxicity commonly induced by chemotherapeutic agents. In animal models of CIPN, ALC administration promoted the recovery of nerve conduction velocity, restored the mechanical nociceptive threshold, and induced analgesia by up-regulating the expression of type-2 metabotropic glutamate receptors in dorsal root ganglia. These results, plus the favourable safety profile of ALC in neuropathies of other aetiologies, have led to the effects of ALC on CIPN being investigated in cancer patients. Preliminary results have confirmed the reasonably good tolerability profile and the efficacy of ALC on CIPN. The present studies support the use of ALC in cancer patients with persisting neurotoxicity induced by paclitaxel or cisplatin treatment.
 ...
PMID:Acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy: a short review. 1769 92

The anesthetic gas nitrous oxide (N2O) and the volatile anesthetic isoflurane (ISO) are commonly used in surgical procedures for human infants and in veterinary and laboratory animal practice to produce loss of consciousness and analgesia. Recent reports indicate that exposure of the developing brain to general anesthetics that block N-methyl-D-aspartate (NMDA) glutamate receptors or potentiate GABA(A) receptors can trigger widespread apoptotic neurodegeneration. In the present study, the question arises whether a relatively low dose of ISO alone or its combination with N2O entails significant risk of inducing enhanced apoptosis. In addition, the role of L-carnitine to attenuate these effects was also examined. Postnatal day 7 (PND-7) rat pups were exposed to N2O (75%) or a low dose of ISO (0.55%) alone, or N2O plus ISO for 2, 4, 6 or 8 h with or without L-carnitine. The neurotoxic effects were evaluated 6 h after completion of anesthetic administration. No significant neurotoxic effects were observed for the animals exposed to N2O or ISO alone. However, enhanced apoptotic cell death was apparent when N2O was combined with ISO at exposure durations of 6 h or more. Co-administration of L-carnitine (300 or 500 mg/kg, i.p.) effectively protected neurons from the anesthetic-induced damage. These data indicate that 6 h or more of inhaled anesthetic exposure consisting of a combination of N2O and ISO results in enhanced neuronal apoptosis, and L-carnitine effectively blocks the neuronal apoptosis caused by inhalation anesthetics in the developing rat brain.
 ...
PMID:The effects of L-carnitine on the combination of, inhalation anesthetic-induced developmental, neuronal apoptosis in the rat frontal cortex. 1820 36