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)

The effects of the tricyclic antidepressants desipramine HCI and chlorimipramine HCI on buprenorphine HCI antinociceptive activity were studied in mice using the hot-plate and the tail-flick methods. In the hot-plate test, desipramine caused a transient antinociceptive effect at low doses, but it decreased buprenorphine analgesia. Chlorimipramine in this test caused a more sustained antinociceptive effect, especially at relatively higher doses, and it did not significantly change buprenorphine analgesia. In the tail-flick test, desipramine either reduced or increased the tail-flick latency in a dose-specific manner, and chlorimipramine (10 mg/kg) significantly increased the tail-flick latency. Desipramine (1 mg/kg) caused a decrease followed by an increase in buprenorphine analgesia. Desipramine (5 and 10 mg/kg) caused significant increases in buprenorphine analgesia. All doses of chlorimipramine (1, 5 and 10 mg/kg) caused significant increases in buprenorphine analgesia. Thus, depending on the test employed, buprenorphine analgesia was modified differently by these tricyclics. Biochemical data suggested a greater role for brain 5-hydroxytryptamine (5-HT) than noradrenaline in tricyclic analgesia.
 ...
PMID:Effects of desipramine and chlorimipramine on buprenorphine analgesia in mice. 374 63

In a double-blind, placebo-controlled study the analgesic efficacy of the combination of a tricyclic antidepressant and morphine was investigated. One of two tricyclic antidepressants (either amitriptyline, a relatively selective serotonin uptake inhibitor or desipramine, a relatively selective noradrenaline uptake inhibitor) or a placebo, was given for 1 week prior to surgery, followed by a single postoperative dose of morphine. Desipramine, but not amitriptyline, both increased and prolonged morphine analgesia. Neither tricyclic antidepressant reduced dental postoperative pain in the absence of morphine. We propose that desipramine enhances opiate analgesia by enhancing a noradrenergic component that contributes to endogenous opioid-mediated analgesia systems.
 ...
PMID:Desipramine enhances opiate postoperative analgesia. 378 63

Like other stress responses, cold-water swim (CWS) analgesia can be altered by changes in norepinephrine (NE) availability. While clonidine pretreatment potentiates CWS analgesia, lesions placed in the noradrenergic locus coeruleus reduce this response. Desipramine (DMI) can alter both the availability and receptor function of catecholamines, particularly NE: while both acute and chronic DMI treatments decrease NE reuptake, subsensitivity of beta-adrenergic receptors occurs only after chronic DMI treatment. The present study examined whether acute and chronic DMI treatments differentially alter CWS analgesia as measured by the jump test, CWS hypothermia and basal jump thresholds. The first experiment determined that pretreatment at either 24, 5 and 1 hr or only at 1 hr with DMI doses of 20 and 5 but not 1 mg/kg potentiated CWS analgesia. The second experiment found that chronic DMI pretreatment at a dose of 10 mg/kg administered twice daily over seven days failed to alter CWS analgesia at 1, 24, 48 or 72 hr thereafter. Neither CWS hypothermia nor basal jump thresholds were affected by the acute or chronic DMI injection regimens. The selective potentiation of CWS analgesia by acute DMI pretreatment is discussed in terms of the differential actions of acute and chronic injection regimens upon NE availability, receptor function, and adaptation processes.
 ...
PMID:Potentiation of cold-water swim analgesia by acute, but not chronic desipramine administration. 408 Jul 60

Neuropathic pain is a chronic condition that is challenging to treat. It often produces considerable physical disability and emotional distress. Patients with neuropathic pain often experience depression and anxiety both of which are known to be temporally correlated with noradrenergic dysfunction in the locus coeruleus (LC) as pain becomes chronic. Antidepressants are the first-line drug therapy for neuropathic pain, and the LC represents a potential target for such therapy. In this study, we evaluated the efficacy of the tricyclic antidepressant desipramine (DMI, a noradrenaline reuptake inhibitor) in preventing or relieving the noradrenergic impairment induced by neuropathic pain. The treatment started before or after the onset of the anxiodepressive phenotype ("early or late treatment") in adult rats subjected to chronic sciatic constriction. Electrophysiological and western blotting assays showed LC dysfunction (increased bursting activity, alpha2-adrenoceptor sensitivity, tyrosine hydroxylase, and noradrenaline transporter expression) in chronic constriction injury at long term. These noradrenergic changes were concomitant to the progression of anxiety and despair-like features. Desipramine induced efficient analgesia, and it counteracted the despair-like behavior in chronic constriction injury-DMI animals, reducing the burst rate and tyrosine hydroxylase expression. Surprisingly, "early" DMI treatment did not modify pain-induced anxiety, and it dampened pain aversion, although these phenomena were abolished when the treatment commenced after noradrenaline impairment had been established. Hence, DMI seems to produce different outcomes depending when the treatment commences, indicating that the balance between the benefits and adverse effects of DMI therapy may shift as neuropathy progresses.
 ...
PMID:The onset of treatment with the antidepressant desipramine is critical for the emotional consequences of neuropathic pain. 3013 Mar 2