Pain modulation by adrenergic agents and morphine as measured by three pain tests

Dennis, Stephen G.; Melzack, Ronald; Gutman, Samuel J.; Boucher, Françoise

doi:10.1016/0024-3205(80)90070-3

Cited by 148 publications

(31 citation statements)

References 24 publications

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“…It is well known that α 2 -adrenergic agents produce antinociception and analgesia (Dennis et al, 1980;Kayser et al, 1992;Paalzow, 1974;Pertovaara, 1993;Reddy et al, 1980;Tasker and Melzack, 1989;Yaksh, 1985). As expected based on its' pharmacokinetic profile, clonidine administration (0.2 mg/kg, i.p.)…”

Section: Discussionmentioning

confidence: 99%

“…The prototypical α 2 -adrenergic agonist clonidine is widely known to elicit antinociception in experimental models of pain (Dennis et al, 1980;Kayser et al, 1992;Paalzow, 1974;Pertovaara, 1993;Reddy et al, 1980;Tasker and Melzack, 1989;Yaksh, 1985). However, its clinical applications are limited due to side-effects such as sedation, sympatholysis, and anxiolysis (Eisenach et al, 1996;Kawamata et al, 1997;Lakhlani et al, 1997;Martin and Eisenach, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Antinociception mediated by α2-adrenergic activation involves increasing tumor necrosis factor α (TNFα) expression and restoring TNFα and α2-adrenergic inhibition of norepinephrine release

et al. 2007

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The central component that establishes chronic pain from peripheral nerve injury is associated with increased tumor necrosis factor-α (TNFα) production in the brain. This study examined TNFα and its reciprocally permissive role with α 2 -adrenergic activation during peak and progressive decline of thermal hyperalgesia in sciatic nerve chronic constriction injury (CCI). Accumulation of TNFα mRNA (in situ hybridization) increases in the hippocampus and locus coeruleus during the onset of neuropathic pain and persists as hyperalgesia abates. Activation of α 2 -adrenergic receptors in control rats decreases TNFα mRNA accumulation in these brain regions. In contrast, during hyperalgesia, α 2 -adrenergic activation enhances TNFα mRNA accumulation. Whether this enhanced TNFα production is associated with changes in the regulation of norepinephrine (NE) release was tested. Hippocampal slices were electrically depolarized to evaluate α 2 -adrenergic and TNFα regulation of NE release. While inhibition of NE release by TNFα is maximal during peak hyperalgesia, it subsequently transforms to facilitate NE release. In addition, α 2 -adrenergic receptor activation with clonidine (0.2 mg/kg, i.p.) in CCI rats experiencing hyperalgesia restores TNFα and α 2 -adrenergic inhibition of NE release. While TNFα directs the development of hyperalgesia, it also directs its resolution. Transformed sensitivity to α 2 -adrenergic agonists during hyperalgesia demonstrates a mechanism for therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antinociception mediated by α2-adrenergic activation involves increasing tumor necrosis factor α (TNFα) expression and restoring TNFα and α2-adrenergic inhibition of norepinephrine release

et al. 2007

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“…The antagonistic effect of yohimbine on morphine analgesia was also shown by the tail flick test in rats (3). In contrast, Dennis et al (4) reported that yohimbine increased morphine analgesia in the hot-plate test and produced a slight degree of analgesic activity by itself. Cicero et al (5) also reported the analgesic effect of phentolamine and its enhancement of morphine analgesia in rats by the hot-plate method.…”

Section: Discussionmentioning

confidence: 89%

Important Role of Adrenergic Function in the Development of Analgesic Tolerance to Morphine in Mice

Kihara

Kaneto

1986

Japanese Journal of Pharmacology

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Abstract-The involvement of a catecholaminergic mechanism in the production of morphine analgesia and the development of tolerance to the effect has been suggested.Here, using various adrenergic blockers, the role of adrenergic function in the mechanism was examined.Phentolamine (a1 +a2-blocker, 10, 1 and 0.5 mg/kg), prazosin (a1 -blocker, 0.1 and 0.02 mg/kg), propranolol ((31 +Q2-blocker, 10, 1 and 0.5 mg/kg), metoprolol (191-blocker, 10 and 1 mg/kg) did not affect morphine analgesia, but dose-dependently suppressed the development of tolerance to morphine.Yohimbine (a2-blocker, 5 and 1 mg/kg) dose-dependently an tagonized morphine analgesia in naive animals and delayed the development of tolerance to morphine. Pindolol (131 +(32-blocker but is devoid of membrane stabilizing activity) suppressed the development of tolerance to morphine analgesia; however, d-propranolol, which possesses membrane stabilizing activity but lacks (3-blocking activity, could not prevent the development of tolerance. Thus, the suppressive effect of propranolol on the development of tolerance is not due to membrane stabilizing properties.Not only the non-selective adrenergic blockers, phentolamine and propranolol, but also the selective blockers of each receptor subtype, prazosin and metoprolol, suppressed the development of tolerance. This fact may suggest the importance of the equilibrated state of adrenergic functions in the mechanism for the development of tolerance to morphine.

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“…The tail-withdrawal test reflects spinal responses while the hot plate method determines supraspinal responses to painful stimulus (Dennis et al, 1980). Aging may cause a more profound decline in opioid system at supraspinal level than at spinal level, and therefore, account for the reported differences in pain parameters.…”

Section: Discussionmentioning

confidence: 99%

Oxidative damage and sensitivity to nociceptive stimulus and opioids in aging rats

Raut

Ratka

2009

Neurobiology of Aging

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Oxidative stress contributes to aging and may cause alterations in pain and analgesia. Knowledge about effects of oxidative stress on the opioid system is very limited. This project was designed to determine the relationship between age-related oxidative damage and opioid antinocicpetion. Three age groups of male Fischer 344 rats were tested for pain sensitivity and responses to morphine and fentanyl using the hot plate method. Oxidative stress markers in various brain regions were measured. With advancing age, nociceptive threshold and antinociceptive effects of opioids decreased significantly. There was a significant negative correlation between morphine antinociception and protein oxidation in cortex, striatum, and midbrain (r 2 = 0.73, 0.87, and 0.77, respectively), and lipid peroxidation in cerebral cortex, hippocampus, and striatum (r 2 = 0.73, 0.61 and 0.71, respectively). Similar correlation was observed between oxidative stress markers and fentanyl antinociception. These findings demonstrate that the age-related increase in oxidative damage in brain is associated with a significant decrease in the antinociceptive effects of opioids.

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Pain modulation by adrenergic agents and morphine as measured by three pain tests

Cited by 148 publications

References 24 publications

Antinociception mediated by α2-adrenergic activation involves increasing tumor necrosis factor α (TNFα) expression and restoring TNFα and α2-adrenergic inhibition of norepinephrine release

Antinociception mediated by α2-adrenergic activation involves increasing tumor necrosis factor α (TNFα) expression and restoring TNFα and α2-adrenergic inhibition of norepinephrine release

Important Role of Adrenergic Function in the Development of Analgesic Tolerance to Morphine in Mice

Oxidative damage and sensitivity to nociceptive stimulus and opioids in aging rats

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