Ultralow dose fentanyl prevents development of chronic neuropathic pain in rats.

Background: Opioids may cause progressive enhancement of pain sensitivity (opioid-induced hyperalgesia [OIH]) and thus, exacerbate existing pain. Animal studies also demonstrate paradoxical OIH with an ultralow dose (ULD, subanalgesic) of opioid; eg, the μ-opioid, morphine. Repeated administration of ULD-morphine resulted in tolerance to ULD-OIH.

Opioid-induced hyperalgesia and burn pain.

The treatment of pain produced during the management of burn injury has been an ongoing problem for physicians caring for these patients. The main therapeutic option for analgesia has been the repeated and prolonged use of opioids. The adverse effects of opioids are well known but the long term use of opioids which produces tolerance with accompanying dose escalation and dependence is most problematic.

Novel small molecule α9α10 nicotinic receptor antagonist prevents and reverses chemotherapy-evoked neuropathic pain in rats.

Background: Peripheral neuropathy is a common dose-limiting side effect of chemotherapy. There are no clinically proven analgesics for the treatment of this condition. Drugs from different classes have been tested with mixed results.

Effect of prior treatment with ultra-low-dose morphine on opioid- and nerve injury-induced hyperalgesia in rats.

Background: In addition to producing analgesia, opioids can increase sensitivity to pain (opioid-induced hyperalgesia [OIH]) in humans and rodents. Tolerance/OIH is likely mediated by similar mechanisms that lead to development of hyperalgesia after nerve injury (neuropathic pain). OIH may be a reason for loss of opioid efficacy and/or a worsening of pain.

The novel small molecule α9α10 nicotinic acetylcholine receptor antagonist ZZ-204G is analgesic.

Chronic pain is inadequately managed with currently available classes of analgesic drugs. Recently, peptide antagonists of the α9α10 nicotinic acetylcholine receptor were shown to be analgesic. The present study was conducted to characterize a novel small molecule, non-peptide antagonist at nicotinic receptors.

Priapism following a lumbar sympathetic nerve block.

Objective: To understand an unusual complication of a common procedure.

Design: This article chronicles the side effect of a lumbar sympathetic nerve block (LSNB).

Setting: Loyola University Medical Center Outpatient Chronic Pain Clinic.

Discovery of non-peptide, small molecule antagonists of α9α10 nicotinic acetylcholine receptors as novel analgesics for the treatment of neuropathic and tonic inflammatory pain.

A series of azaaromatic quaternary ammonium analogs has been discovered as potent and selective α9α10 nicotinic acetylcholine receptor (nAChR) antagonists. The preliminary structure-activity relationships of these analogs suggest that increased rigidity in the linker units results in higher potency in inhibition of α9α10 nAChRs and greater selectivity over α7 nAChRs. These analogs represent a new class of analgesic for the treatment of neuropathic and tonic inflammatory pain.

Buprenorphine-induced hyperalgesia in the rat.

In addition to analgesia opioids may also enhance pain sensitivity. Opioid-induced hyperalgesia, typically associated with potent mu-opioid agonists (e.g.

Antinociceptive effects and toxicity of morphine-6-O-sulfate sodium salt in rat models of pain.

Mu-opioids (i.e. morphine, oxycodone, hydrocodone) are considered to be the primary drugs for treatment of moderate to severe acute, chronic and cancer pain.

The analgesic and toxic effects of nornicotine enantiomers alone and in interaction with morphine in rodent models of acute and persistent pain.

Neuronal nicotinic acetylcholinic receptors (nAChR) are promising targets for the development of novel analgesics. Nicotine and other nAChR-agonists produce profound analgesia in rodent models of acute and persistent pain. However, significant side-effects are of concern.

The relative abuse liability of oral oxycodone, hydrocodone and hydromorphone assessed in prescription opioid abusers.

Abuse of prescription opioids has risen precipitously in the United States. Few controlled comparisons of the abuse liability of the most commonly abused opioids have been conducted. This outpatient study employed a double-blind, randomized, within-subject, placebo-controlled design to examine the relative abuse potential and potency of oral oxycodone (10, 20 and 40 mg), hydrocodone (15, 30 and 45 mg), hydromorphone (10, 17.

Effects of norketamine enantiomers in rodent models of persistent pain.

NMDA-receptor antagonists are potential drugs for chronic pain treatment, in particular for neuropathic pain involving central sensitization processes. Clinical use of available NMDA antagonists, such as ketamine, is limited for this indication due to its side effects (psychotomimetic, sedative, motor). There is a need for novel NMDA-receptor antagonist(s) with better analgesia/toxicity profile(s).

Interaction between morphine and norketamine enantiomers in rodent models of nociception.

Ketamine, one of a few clinically-available N-Methyl-D-aspartate (NMDA)-receptor antagonists, is known to improve the analgesic efficacy of opioids in humans and rodents. However, the use of ketamine in combination with opioids is mainly restricted to the perioperative setting, due to severe psychotomimetic, sedative and motor side effects. Recent data from our laboratory demonstrated that a major metabolite of ketamine, norketamine, in particular the S(+) enantiomer, had a better antinociception/side effects profile than ketamine in rats.

Characterization of the antinociceptive and pronociceptive effects of methadone in rats.

Background: Recently, it has been appreciated that in addition to their antinociceptive properties, opioid analgesics also can enhance pain sensitivity (opioid-induced hyperalgesia [OIH]). OIH may enhance preexisting pain and contribute to dose escalation, tolerance, and misuse/abuse of opioids. Better information is needed to determine which opioid or opioid combinations may be least likely to produce OIH and therefore possibly represent better choices for pain management.

Characterization of the antinociceptive effect of oxycodone in male and female rats.

A number of investigators have shown that sex plays an important role in the analgesic effects of opioids. Typically, the antinociceptive responsiveness to mu opioid agonists such as morphine is greater in male than in female rats. The effect of sex on kappa opioid analgesia is less known.

Characterization of morphine-induced hyperalgesia in male and female rats.

The pain enhancing (hyperalgesic) effect of morphine was characterized in relation to pain stimulus (thermal, mechanical), dose, mode of administration (acute, chronic), sex and mechanism. We found that a low (subanalgesic) dose of morphine enhanced the sensitivity to thermal and mechanical noxious stimuli in a dose- and sex-related manner. Morphine hyperalgesia was inversely related to dose (0.

Morphine tolerance in male and female rats.

Several studies indicate greater sensitivity to morphine (MOR) analgesia in male compared to female rats under the acute dosing condition. The present study investigated whether the same sex difference in sensitivity persists in MOR-tolerant rats. MOR was administered chronically (7 mg/kg twice daily) until tolerance developed in each rat.

Sex-related differences in the enhancement of morphine antinociception by NMDA receptor antagonists in rats.

The effect of the N-methyl-D-aspartate (NMDA) receptor antagonists dextromethorphan (DEX), ketamine (KET), and MK-801 on morphine (MOR)-induced antinociception has been investigated in male and female rats. DEX (7.5, 15, and 30 mg/kg), KET (0.

The effects of flumazenil on the antinociceptive actions of morphine in rats.

The 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazol[1,5-a][1,4]benzodiazepine-3-carboxylic acid ethyl ester (Flumazenil)-morphine interaction on analgesia (acute pain model, tail-flick test) was tested after intraperitoneal (IP) and intrathecal (IT) routes of administration in female rats. Analgesia was enhanced by the concurrent administration of Flumazenil with morphine (IP), in a dose-related way. Flumazenil alone (IP) did not produce analgesia.

Modification of morphine analgesia and tolerance by flumazenil in male and female rats.

This study assessed the effect of the central benzodiazepine receptor antagonist, 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid ethyl ester (flumazenil), on morphine-induced analgesia, locomotor effects, and development of tolerance in rats. The thermally evoked pain (tail flick) response was determined after acute and chronic intraperitoneal (i.p.