Morphine hyperalgesia in mice is unrelated to opioid activity, analgesia, or tolerance: Evidence for multiple diverse hyperalgesic systems

Juni, Aaron; Klein, Gad; Kest, Benjamin

doi:10.1016/j.brainres.2005.11.054

Cited by 53 publications

(67 citation statements)

References 34 publications

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“…Opiate and nicotine-induced analgesic tolerance can be blocked with the administration of non-selective opioid and nicotinic receptor antagonists [23]. However, the hyperalgesic effects of chronic opiate administration are not due to the activation of opiate receptors [15] and tolerance to the antinociceptive effects of subcutaneous nicotine can be blocked with the co-administration of an NMDA receptor antagonist [14].…”

Section: Discussionmentioning

confidence: 99%

“…Paw withdrawal measurements were performed on days 5 and 14 post-osmotic pump implantation. On day 14 post-pump implantation, paw withdrawal thresholds of rats receiving 8.6 mg/kg/ day nicotine were measured at least 1 hour prior to the intrathecal administration of undiluted polyclonal anti-dynorphin A [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] antiserum (Oncogene, San Diego, CA) or normal rabbit serum (NRS). Paw withdrawal thresholds were measured by an observer blinded to treatment at 30 and 60 minutes post-dynorphin antiserum/NRS administration.…”

Section: Behavioral Testingmentioning

confidence: 99%

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Increased spinal dynorphin contributes to chronic nicotine-induced mechanical hypersensitivity in the rat

Lough

Young

Parker

et al. 2007

Neuroscience Letters

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Chronic nicotine administration has been shown previously to produce mechanical hypersensitivity in the rat although the mechanism of this effect is unknown. Rats treated with chronic systemic nicotine 3.6 or 8.6 mg/kg/day for 14-21 days displayed mechanical hypersensitivity coincident with an increase of prodynorphin immunoreactivity and dynorphin content within the spinal cord. The administration of dynorphin antiserum intrathecally significantly attenuated chronic nicotineinduced mechanical hypersensitivity. Our results suggest that chronic nicotine administration produces an increase in spinal dynorphin content and release that contributes to mechanical hypersensitivity.

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Section: Discussionmentioning

confidence: 99%

Section: Behavioral Testingmentioning

confidence: 99%

Increased spinal dynorphin contributes to chronic nicotine-induced mechanical hypersensitivity in the rat

Lough

Young

Parker

et al. 2007

Neuroscience Letters

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“…Ackerman [40] described a similar outcome in 28 % of a sample of 197 patients with chronic pain receiving opioids. While some studies suggest that OIH develops after chronic opioid use [41][42][43], both rodent [44,45] and human studies [46][47][48][49] have documented OIH within hours of acute opioid administration. Studies using shorter-acting opioids such as remifentanil, sufentanil, fentanyl, and morphine provide the most suspicion of OIH [49][50][51][52][53][54][55][56]; however, there is documentation of this phenomenon in patients receiving long-acting opioids (e.g., methadone or buprenorphine) as well [23,43,[57][58][59][60].…”

Section: Prevalence Of Oih In Humansmentioning

confidence: 99%

Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations

et al. 2015

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Opioid analgesics have become a cornerstone in the treatment of moderate to severe pain, resulting in a steady rise of opioid prescriptions. Subsequently, there has been a striking increase in the number of opioid-dependent individuals, opioid-related overdoses, and fatalities. Clinical use of opioids is further complicated by an increasingly deleterious profile of side effects beyond addiction, including tolerance and opioid-induced hyperalgesia (OIH), where OIH is defined as an increased sensitivity to already painful stimuli. This paradoxical state of increased nociception results from acute and long-term exposure to opioids, and appears to develop in a substantial subset of patients using opioids. Recently, there has been considerable interest in developing an efficacious treatment regimen for acute and chronic pain. However, there are currently no well-established treatments for OIH. Several substrates have emerged as potential modulators of OIH, including the N-methyl-D-aspartate and γ-aminobutyric acid receptors, and most notably, the innate neuroimmune system. This review summarizes the neurobiology of OIH in the context of clinical treatment; specifically, we review evidence for several pathways that show promise for the treatment of pain going forward, as prospective adjuvants to opioid analgesics. Overall, we suggest that this paradoxical state be considered an additional target of clinical treatment for chronic pain.

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“…11 Subcutaneous morphine (at B 3 mgÁkg -1 ) has been shown to block peripheral mechanical allodynia without sedation, allowing us to use morphine as a control for the presence of non-specific peripheral mechanical allodynia. 5,10,12 To examine the Table Relative allodynia Three groups of six pairs assessed for significance using the binomial test.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a novel mouse model of intracisternal strychnine-induced trigeminal allodynia

Whitehead

Ries

Schwarz

et al. 2013

Can J Anesth/J Can Anesth

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Purpose Intractable neuropathic dynamic allodynia remains one of the major symptoms of human trigeminal neuropathy and is commonly accepted to be the most excruciatingly painful condition known to humankind. At present, a validated animal model of this disorder is necessary for efficient and effective development of novel drug treatments. Intracisternal strychnine in rats has been shown to result in localized trigeminal dynamic allodynia, thus representing a possible model of trigeminal neuralgia. The purpose of this study was to validate a mouse model of trigeminal glycinergic inhibitory dysfunction using established positive (carbamazepine epoxide) and negative (morphine) controls. MethodsThe actions of conventional first-line treatment (carbamazepine epoxide [CBZe]) and clinically ineffective morphine were tested for trigeminal dynamic mechanical allodynia produced by intracisternal strychnine. In mice under halothane anesthesia, we injected either strychnine (0.3 lg), strychnine with CBZe (4 ng), or artificial cerebrospinal fluid (aCSF) intracisternally (i.c.). In a separate set of experiments, subcutaneous morphine (3 mgÁkg -1 sc) was injected with intracisternal strychnine. Dynamic mechanical allodynia was induced by stroking the fur with polyethylene (PE-10) tubing. The response of each mouse was rated to determine its allodynia score, and scores of each group were compared. In addition, in a separate dichotomous disequilibrium study, pairs of mice were injected with strychnine/saline, strychnine/strychnine-CBZe, or strychnine/strychnine-morphine. A blinded observer recorded which mouse of each pair had the greater global pain behaviour. Results Strychnine (i.c.) produced higher quantitative allodynia scores in the trigeminal distribution (mean 81.5%; 95% confidence interval [CI] 76.4 to 86.6) vs the aCSF group (mean 11.3%; 95% CI 8.1 to 14.4) (P \ 0.0001). Carbamazepine epoxide (i.c.) completely abolished allodynia when co-injected with strychnine (mean 83.2%; 95% CI 78.1 to 88.4) vs strychnine alone (mean 3.2%; 95% CI -0.9 to 7.2) (P \ 0.0001). Morphine co-injected with strychnine did not result in reduced allodynia (mean 65.7%; 95% CI 42.0 to 89.4) compared with strychnine alone (mean 87.6%; 95% CI 77.6 to 97.6) (P = 0.16). In a further global allodynia assessment, strychnine (i.c.) produced greater allodynia than both aCSF and strychnine administered with CBZe (P = 0.03). Morphine (ip) administered with strychnine did not result in reduced global allodynia compared with strychnine administered alone (P = 1.0).Author contributions Il-Ok Lee performed the experiments. Il-Ok Lee, Craig R. Ries, Stephan K.W. Schwarz, Ernest Puil, and Bernard A. MacLeod contributed to the experimental design and the rationale for the experiments. Ryan A. Whitehead contributed to data analysis and the writing of the manuscript. Craig R. Ries, Stephan K.W. Schwarz, and Ernest Puil edited the manuscript. Bernard A. MacLeod initiated the project and participated in the experimental techniques and in the preparation an...

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Morphine hyperalgesia in mice is unrelated to opioid activity, analgesia, or tolerance: Evidence for multiple diverse hyperalgesic systems

Cited by 53 publications

References 34 publications

Increased spinal dynorphin contributes to chronic nicotine-induced mechanical hypersensitivity in the rat

Increased spinal dynorphin contributes to chronic nicotine-induced mechanical hypersensitivity in the rat

Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations

Evaluation of a novel mouse model of intracisternal strychnine-induced trigeminal allodynia

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