Attenuation of hyperalgesia in a rat model of neuropathic pain after intrathecal pre- or post-treatment with a neurokinin-1 antagonist

Cahill, Catherine M.; Coderre, Terence J.

doi:10.1016/s0304-3959(01)00410-9

Cited by 88 publications

(66 citation statements)

References 49 publications

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“…110 Moreover, spinal administration of the NK1 receptor antagonist L-732,138 fully reversed thermal hypersensitivity in rats receiving sustained morphine treatment via a subcutaneous morphine-pellet implant. 111 Interestingly, morphine-induced hyperalgesia was not observed in NK1 receptor knockout (NK1 Ϫ/Ϫ ) mice, providing evidence for a critical involvement of the NK1 receptor in the manifestation of morphine-induced hyperalgesia. These spinal NK1 expressing neurons are at the origin of the input pathways into midbrain and brainstem modulatory systems.…”

Section: Opioid-induced Hyperalgesiamentioning

confidence: 99%

Preclinical and Early Clinical Investigations Related to Monoaminergic Pain Modulation

2009

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Summary:The balance between descending controls, both excitatory and inhibitory, can be altered in various pain states. There is good evidence for a prominent ␣ 2 -adrenoceptor-mediated inhibitory system and 5-HT 3 (and likely also 5-HT 2 ) serotonin receptor-mediated excitatory controls originating from brainstem and midbrain areas. The ability of cortical controls to influence spinal function allows for top-down processing through these monoamines. The links between pain and the comorbidities of sleep problems, anxiety, and depression may be due to the dual roles of noradrenaline and of 5-HT in these functions and also in pain. These controls appear, in the cases of peripheral neuropathy, spinal injury, and cancer-induced bone pain to be driven by altered peripheral and spinal neuronal processes; in opioid-induced hyperalgesia, however, the same changes occur without any pathophysiological peripheral process. Thus, in generalized pain states in which fatigue, mood changes, and diffuse pain occur, such as fibromyalgia and irritable bowel syndrome, one could suggest an abnormal engagement of descending facilitations with or without reduced inhibitions but with central origins. This would be an endogenous central malfunction of top-down processing, with the altered monoamine systems underlying the observed symptoms. A number of analgesic drugs can either interact with or have their actions modulated by these descending systems, reinforcing their importance in the establishment of pain but also in its control. Key Words: 5-HT receptors, 5-HT, serotonin, noradrenaline, RVM, rostral ventromedial medulla, opioidinduced hyperalgesia, neuropathy, fibromyalgia. PAIN, COMORBIDITIES, AND MONOAMINESPain and mood share certain neurological pathways in the CNS and have overlapping neurochemical bases, in particular their modulation by monoamine systems. This provides the substrate through which pain can influence mood, giving rise to comorbidities or secondary symptoms such as anxiety and depression, 1,2 and by the same continuum allows mood to exacerbate pain; indeed, patients with depression often present with symptoms that include medically unexplained pain, with the mean prevalence of such occurrence cited as 65%.1,3 Emotional facets of nociception play a significant role in the pain experience, with fear largely driving adaptive behaviors that enable avoidance of actual or impending harm. This therefore subserves the key function of pain, to protect the integrity and survival of an organism. Moreover, the role of emotions and state of mind in pain partly underlie the variable relationship between the intensity of damaging stimuli and perceived pain, such that at any given time and for any given nociceptive stimulus, painful response can be influenced by emotional state (the psychological context in which the stimulus is received), emotional trait (the psychological characteristics of the recipient), and cognitive set (attention and vigilance, for example).Depression is associated with abnormalities in the monoaminergic ...

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Section: Opioid-induced Hyperalgesiamentioning

confidence: 99%

Preclinical and Early Clinical Investigations Related to Monoaminergic Pain Modulation

2009

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“…Although L-732,138 has been shown to have higher affinity for the cloned human receptor compared to the cloned rat receptor (200-fold difference), L-732,138 has been shown to have specificity for the NK-1 receptor, showing greater than 1000-fold higher affinity to the NK-1 receptor compared to the NK-2 or NK-3 receptors (Cascieri et al, 1994). This antagonist has the additional advantage of not antagonizing calcium channels, as has been reported with some other NK-1 receptor antagonists (Cahill and Coderre, 2002). The dose used in this study was based on previous studies done with this antagonist in rats (Cahill and Coderre, 2002).…”

Section: Cannulation and Drug Administrationmentioning

confidence: 99%

“…This antagonist has the additional advantage of not antagonizing calcium channels, as has been reported with some other NK-1 receptor antagonists (Cahill and Coderre, 2002). The dose used in this study was based on previous studies done with this antagonist in rats (Cahill and Coderre, 2002).…”

Section: Cannulation and Drug Administrationmentioning

confidence: 99%

“…In order to determine whether the NK-1 receptor plays a role in sustained morphine-induced thermal hypersensitivity, a selective NK-1 receptor antagonist L-732,138 (Cahill and Coderre, 2002), was evaluated for possible reversal of morphine-induced thermal hypersensitivity in rats. Pawwithdrawal latencies were determined in rats prior to implantation of morphine or placebo pellets and again 6 h, 2 and 6 days after pellet implantation.…”

Section: Nk-1 Receptor Antagonist In Ratsmentioning

confidence: 99%

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Role of NK-1 neurotransmission in opioid-induced hyperalgesia

King

Gardell

Wang

et al. 2005

Pain

153

128

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Opiates are among the most important drugs for treatment of moderate to severe pain and prolonged opiate administration is often required to treat chronic pain states. We investigated the neurobiological actions of sustained opiate administration revealing paradoxical pronociceptive adaptations associated with NK-1 receptor function. Sustained morphine delivered over 6 days elicited hyperalgesia in rats and mice during the period of opiate delivery. Sustained morphine administration increased substance P (SP) and NK-1 receptor expression in the spinal dorsal horn. Sustained morphine treatment also enhanced capsaicin-evoked SP release in vitro, and increased internalization of NK-1 receptors in response to noxious stimulation. While NK-1 receptor internalization was observed primarily in the superficial laminae of placebo-treated rats, NK-1 receptor internalization was seen in both superficial and deep lamina of the dorsal horn in morphinetreated animals. Morphine-induced hyperalgesia was reversed by spinal administration of an NK-1 receptor antagonist in rats and mice, and was observed in wildtype (NK-1 +/+ ), but not NK-1 receptor knockout (NK-1 −/− ), mice. These data support a critical role for the NK-1 receptor in the expression of sustained morphine-induced hyperalgesia. Additionally, these data indicate that sustained opiate administration induces changes reminiscent of those associated with inflammatory pain. These opiate-induced changes might produce unintended deleterious actions in the course of pain treatment in patients. Understanding of sustained morphine-induced neurochemical changes will help identify approaches that limit the deleterious actions of opiates.

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“…Evidence suggests this is due to grafted NSCs exhibiting trophic and reparative effects. 34 In support of this, the correlation between NSC administration and anti-nociceptive effects were associated with: a rapid decrease in Fos expression in laminae I-VI -high levels are normally associated with neuronal activity following noxious stimulation; 35 a decrease in immunoreactivity for substance P in the same region -substance P has been associated with increased neuropathic pain in rodents; 36 and a reduction in mRNA levels of the proinflammatory pro-algesic cytokines IL-1 and IL-6, coupled with a rise in mRNA levels of the anti-inflammatory cytokine IL-10. These findings suggest that NSCs act as local modifying agents transforming the hostile proinflammatory neurochemical environment associated with nerve injury into a more permissive milieu.…”

Section: Evidence On the Utility Of Adult Stem Cells For The Treatmenmentioning

confidence: 87%

Stem cell therapies for neuropathic pain

Seewoodhary

Harvey

2014

Br J Diabetes

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Neuropathic pain is a large-scale epidemiological problem affecting 13-26% of the diabetic population. The complex aetiology and pathophysiology coupled with the lack of a diagnostic test for the underlying cause renders the assessment of neuropathic pain subjective and the treatment difficult, especially as current licensed treatments are limited in their application towards the attainment of palliation.Cell therapies offer a novel curative therapeutic dimension for neuropathic pain. This is based on replacing damaged neuronal tissue, protecting against progressive nerve damage, and releasing soluble factors that act in a paracrine or endocrine manner, which facilitate repair and reversal of the pathology that underlies the genesis and propagation of damage within the somatosensory system. Cell therapies with potential utility for the treatment of neuropathic pain include embryonic stem cells, adult stem cells and induced pluripotent stem cells.

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Attenuation of hyperalgesia in a rat model of neuropathic pain after intrathecal pre- or post-treatment with a neurokinin-1 antagonist

Cited by 88 publications

References 49 publications

Preclinical and Early Clinical Investigations Related to Monoaminergic Pain Modulation

Preclinical and Early Clinical Investigations Related to Monoaminergic Pain Modulation

Role of NK-1 neurotransmission in opioid-induced hyperalgesia

Stem cell therapies for neuropathic pain

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