Analgesia, enhancement of spinal morphine antinociception, and inhibition of tolerance by ultra-low dose of the α2A-adrenoceptor selective antagonist BRL44408.

Ultra-low doses of non-selective α2-adrenoceptor antagonists augment acute spinal morphine antinociception and block morphine tolerance; however, the receptor involved in mediating these effects is currently unknown. Here, we used tail flick and paw pressure tests on the rat to investigate the acute analgesic and tolerance-inducing effects of spinal morphine and norepinephrine alone or in combination with an ultra-low dose of the α2A-adrenoceptor antagonist, BRL44408. We also assessed the potential antinociceptive effects of BRL44408 alone following spinal administration.

Stereo-selective inhibition of spinal morphine tolerance and hyperalgesia by an ultra-low dose of the alpha-2-adrenoceptor antagonist efaroxan.

Ultra-low doses of alpha-2 (α2)-adrenoceptor antagonists augment spinal morphine antinociception and inhibit tolerance, but the role of receptor specificity in these actions is unknown. We used the stereo-isomers of the α2 adrenoceptor antagonist, efaroxan to evaluate the effect of receptor specificity on the induction of spinal morphine tolerance and hyperalgesia. Tail flick and paw pressure tests were first used to evaluate high dose efaroxan (12.

Intrathecal catheterization influences tolerance to chronic morphine in rats.

We evaluated the antinociceptive effects of acute and chronic morphine administered spinally via lumbar puncture in intrathecally catheterized and sham-surgery rats. The effects of acute morphine did not differ between groups. Catheterized rats developed tolerance to chronic morphine more rapidly, compared with sham and naive rats.

Low dose alpha-2 antagonist paradoxically enhances rat norepinephrine and clonidine analgesia.

Ultralow-dose opioid antagonists prolong opioid antinociception and block tolerance. In this study we determined whether low doses of the α-2 adrenergic receptor (A2-R) antagonist, atipamezole, similarly influenced A2-R-induced antinociception and tolerance. In rats, intrathecal norepinephrine (NE) or clonidine in combination with atipamezole was tested using tail-flick and paw pressure tests.

Inhibition of tolerance to spinal morphine antinociception by low doses of opioid receptor antagonists.

Ultra-low doses of opioid receptor antagonists inhibit development of chronic spinal morphine tolerance. As this phenomenon mechanistically resembles acute tolerance, the present study examined actions of opioid receptor antagonists on acute spinal morphine tolerance. In adult rats, administration of three intrathecal injections of morphine (15 microg) at 90 min intervals produced a significant decline of the antinociceptive effect and loss of agonist potency in both the tail-flick and paw-pressure tests.

Spinal administration of lipoxygenase inhibitors suppresses behavioural and neurochemical manifestations of naloxone-precipitated opioid withdrawal.

1. This study investigated the role of spinal lipoxygenase (LOX) products in the induction and expression of opioid physical dependence using behavioural assessment of withdrawal and immunostaining for CGRP and Fos protein expression in the spinal cord. 2.

The role of spinal neuropeptides and prostaglandins in opioid physical dependence.

This study examined the role of spinal calcitonin gene-related peptide (CGRP), substance P, and prostaglandins in the development and expression of opioid physical dependence. Administration of escalating doses (5 - 100 mg kg-1, i.p.

Analgesia and tolerance to intrathecal morphine and norepinephrine infusion via implanted mini-osmotic pumps in the rat.

The objectives of this study were to investigate the duration of analgesia and the development of tolerance following continuous intrathecal administration of morphine and norepinephrine alone, and morphine followed by norepinephrine via mini-osmotic pumps in the rat. Analgesia was assessed by the tail-flick test. In single pump experiments morphine 1 microliter (10 micrograms)/h (7 days) and 0.