Exogenous and Endogenous Opioid‐Induced Pain Hypersensitivity in Different Rat Strains

Laboureyras, Emilie; Aubrun, Frédéric; Monsaingeon, M.; Corcuff, Jean-Benoı̂t; Laulin, Jean‐Paul; Simonnet, Guy

doi:10.1155/2014/285308

Cited by 16 publications

(9 citation statements)

References 51 publications

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“…Opioid-induced hyperalgesia was particularly evident in the sham rats, but was also clear after SCI on the measure of tactile reactivity. These data are commensurate with other animal 17,[68][69][70][71][72][73] and clinical studies demonstrating that both tolerance and hyperalgesia are commonly encountered among patients using opioids to control pain. 41,[74][75][76][77][78][79][80] While the behavioral effects of repeated opioid administration on hyperalgesia and tolerance are clear, the molecular changes that might mediate these effects are not.…”

supporting

confidence: 80%

Neurobiological Effects of Morphine after Spinal Cord Injury

Hook

Woller

Bancroft

et al. 2017

Journal of Neurotrauma

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Opioids and non-steroidal anti-inflammatory drugs are used commonly to manage pain in the early phase of spinal cord injury (SCI). Despite its analgesic efficacy, however, our studies suggest that intrathecal morphine undermines locomotor recovery and increases lesion size in a rodent model of SCI. Similarly, intravenous (IV) morphine attenuates locomotor recovery. The current study explores whether IV morphine also increases lesion size after a spinal contusion (T12) injury and quantifies the cell types that are affected by early opioid administration. Using an experimenter-administered escalating dose of IV morphine across the first seven days post-injury, we quantified the expression of neuron, astrocyte, and microglial markers at the injury site. SCI decreased NeuN expression relative to shams. In subjects with SCI treated with IV morphine, virtually no NeuN + cells remained across the rostral-caudal extent of the lesion. Further, whereas SCI per se increased the expression of astrocyte and microglial markers (glial fibrillary acidic protein and OX-42, respectively), morphine treatment decreased the expression of these markers. These cellular changes were accompanied by attenuation of locomotor recovery (Basso, Beattie, Bresnahan scores), decreased weight gain, and the development of opioid-induced hyperalgesia (increased tactile reactivity) in morphine-treated subjects. These data suggest that morphine use is contraindicated in the acute phase of a spinal injury. Faced with a lifetime of intractable pain, however, simply removing any effective analgesic for the management of SCI pain is not an ideal option. Instead, these data underscore the critical need for further understanding of the molecular pathways engaged by conventional medications within the pathophysiological context of an injury.

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supporting

confidence: 80%

Neurobiological Effects of Morphine after Spinal Cord Injury

Hook

Woller

Bancroft

et al. 2017

Journal of Neurotrauma

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“…Hyperalgesic priming type 2 is induced by repeated intradermal injection of a µ-opioid receptor agonist (Araldi et al, 2015(Araldi et al, , 2017. Although a form of latent sensitization is induced by overdoses of opioids like fentanyl and remifentanil, its hyperalgesia is additive with the hyperalgesia of latent sensitization induced by paw incision (Campillo et al, 2011) or carrageenan (Rivat et al, 2007;Laboureyras et al, 2014). This suggests that opioid-induced latent sensitization is different from the latent sensitization induced by inflammation, incision or nerve injury.…”

Section: Discussionmentioning

confidence: 99%

A Src family kinase maintains latent sensitization in rats, a model of inflammatory and neuropathic pain

Chen

Marvizón

2020

Brain Research

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Latent sensitization is a long-term model of chronic pain in which hyperalgesia is continuously suppressed by opioid receptors. This is demonstrated by the induction of mechanical allodynia by opioid antagonists. Different intracellular signals may mediate the initiation, maintenance and expression of latent sensitization. Our criterion for the involvement of a signal in the maintenance of latent sensitization is that it inhibitors should permanently eliminate the allodynia produced by an opioid antagonist. We hypothesized that Src family kinases (SFKs) maintain latent sensitization and tested this hypothesis in rats with latent sensitization induced by complete Freund's adjuvant (CFA) or by spared nerve injury. After measures of mechanical allodynia returned to baseline, the SFK inhibitor PP2 or vehicle were injected intrathecally. The opioid antagonist naltrexone injected intrathecally 15 min later produced allodynia in control rats but not in rats injected with PP2. PP2 or vehicle were injected daily for two more days and naltrexone was injected five days later. Again, naltrexone induced allodynia in the control rats but not in the rats injected with PP2. Results were similar when latent sensitization was induced either with CFA or spared nerve injury. We concluded that an SFK, likely Fyn, maintains latent sensitization induced by inflammation or nerve injury. PerspectiveThis article presents evidence that a Src family kinase, likely Fyn, maintains latent sensitization induced by inflammation or nerve injury. If latent sensitization is a valid model of chronic pain, inhibiting its maintenance with Src family kinase inhibitors may cure chronic pain.

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“…OIH was found to be strongest in patients with the met/met catechol-O-methyltransferase polymorphism, which is responsible for markedly greater stress-induced increases in plasma levels of stress axis mediators (Jabbi et al, 2007;Jensen et al, 2009). Patients with preoperative stress are more vulnerable to postoperative pain (Munafo and Stevenson, 2001) and, stress exacerbates OIH (Edwards et al, 2011(Edwards et al, , 2016Laboureyras et al, 2014). Stress also induces hyperalgesic priming (Khasar et al, 2009;Green et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Nociceptor Neuroplasticity Associated with In Vivo Opioid-Induced Hyperalgesia

2019

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Opioid-induced hyperalgesia (OIH) is a serious adverse event produced by opioid analgesics. Lack of an in vitro model has hindered study of its underlying mechanisms. Recent evidence has implicated a role of nociceptors in OIH. To investigate the cellular and molecular mechanisms of OIH in nociceptors, in vitro, subcutaneous administration of an analgesic dose of fentanyl (30 g/kg, s.c.) was performed in vivo in male rats. Two days later, when fentanyl was administered intradermally (1 g, i.d.), in the vicinity of peripheral nociceptor terminals, it produced mechanical hyperalgesia (OIH). Additionally, 2 d after systemic fentanyl, rats had also developed hyperalgesic priming (opioid-primed rats), long-lasting nociceptor neuroplasticity manifested as prolongation of prostaglandin E 2 (PGE 2) hyperalgesia. OIH was reversed, in vivo, by intrathecal administration of cordycepin, a protein translation inhibitor that reverses priming. When fentanyl (0.5 nM) was applied to dorsal root ganglion (DRG) neurons, cultured from opioid-primed rats, it induced a-opioid receptor (MOR)-dependent increase in [Ca 2ϩ ] i in 26% of small-diameter neurons and significantly sensitized (decreased action potential rheobase) weakly IB4 ϩ and IB4 Ϫ neurons. This sensitizing effect of fentanyl was reversed in weakly IB4 ϩ DRG neurons cultured from opioid-primed rats after in vivo treatment with cordycepin, to reverse of OIH. Thus, in vivo administration of fentanyl induces nociceptor neuroplasticity, which persists in culture, providing evidence for the role of nociceptor MOR-mediated calcium signaling and peripheral protein translation, in the weakly IB4-binding population of nociceptors, in OIH.

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Exogenous and Endogenous Opioid‐Induced Pain Hypersensitivity in Different Rat Strains

Abstract: The pain level not only reflects nociceptive inputs but also depends on both the history and genetic factors of the individual. Genetic and environmental models may provide new insights into the mechanisms that underlie individual differences observed in postoperative pain.

Cited by 16 publications

References 51 publications

Neurobiological Effects of Morphine after Spinal Cord Injury

Neurobiological Effects of Morphine after Spinal Cord Injury

A Src family kinase maintains latent sensitization in rats, a model of inflammatory and neuropathic pain

In Vitro Nociceptor Neuroplasticity Associated with In Vivo Opioid-Induced Hyperalgesia

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