Pain MechanismThe role of spinal orexin-1 receptors in posterior hypothalamic modulation of neuropathic pain
Section snippets
Experimental procedures
The Institutional Animal Care Committee at the University of Illinois at Chicago approved the experimental protocols used in this study. The experiments were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publication No. 90–23). All efforts were made to minimize animal suffering, reduce the numbers of animals used, and use alternatives to in vivo experiments.
Results
Of the 89 rats used, 19 were excluded. Three rats showed self-mutilation; five rats did not exhibit neuropathic behaviors on the left affected foot; and 11 rats showed misplacement of either intracranial, intrathecal, or both cannulae.
Discussion
In the present study, we demonstrated that carbachol-induced PH stimulation produced a robust antinociceptive response in female rats with CCI compared to rats given saline in the PH. This antinociceptive response was mediated by cholinergic receptors in the PH, and blocked by intrathecal administration of the OX1R antagonist, SB-334867. While these findings are novel and are suggestive of a direct projection from orexin-containing neurons in the PH to the dorsal horn, we cannot say with
Conclusion
In summary, PH stimulation with carbachol decreased CCI neuropathic pain as demonstrated by increased foot withdrawal latencies. Pretreatment with atropine sulfate blocked PH-induced antinociception. Intrathecal application of an OX1R antagonist significantly decreased foot withdrawal latencies compared to DMSO controls, while the OX1R antagonist given alone had no effect in neuropathic pain. These findings are suggestive that cholinergic muscarinic receptors mediate activation of PH neurons
Acknowledgments
This work was supported by Midwest Nursing Research Society/American Nurses Foundation grant and USPHS grant HHS NR04778 from the National Institute of Nursing Research at the National Institutes of Health.
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Coregulation of sleep-pain physiological interplay by orexin system: An unprecedented review
2020, Behavioural Brain ResearchEffects of intrathecal administration of orexin-1 receptor antagonist on antinociceptive responses induced by chemical stimulation of lateral hypothalamus in an animal model of tonic nociception
2018, NeuropeptidesCitation Excerpt :Moreover, they reported that intrathecal injection of SB-334867 alone had no effect in the formalin test or in the hot plate test. Additionally, Jeong and Holden (2009) have demonstrated the role of spinal orexin-1 receptors in posterior hypothalamus (PH) in modulation of neuropathic pain. However, considering the volume of the carbachol administered, the activation of this area (PH) was lesser than that in the LH.
A review of the role of orexin system in pain modulation
2017, Biomedicine and PharmacotherapyCitation Excerpt :Moreover, in another study the effect of orexin-A on high K+-induced [Ca2+]i increase was attributed to the inhibition of Ca2+ influx through L-type Ca2+ channel in dorsal root ganglion (DRG) neurons of rat segmental spinal nerve ligation (SNL) model, which may have important implications for nociceptive modulation and pain, so that, nifedipine and lidocaine strongly inhibited on the high K+-induced depolarization [Ca2+]i increase in sham and SNL groups, while orexine-A inhibited on the high K+-induced depolarization [Ca2+]i increase in DRG neurons [26]. According to another study, the antinociception effect of orexin-A in a neuropathic pain model in rat (chronic constriction injury) through stimulating the posterior hypothalamus by cholinergic agonist carbachol microinjection is mediated partly via orexin receptor type-1 in the spinal cord dorsal horn [27]. Stress-induced analgesia is a key component of the defensive behavioral reaction to prepare for fight or flight [28].
Modulation of nociception by medial pre-optic area orexin a receptors and its relation with morphine in male rats
2016, Brain Research BulletinCitation Excerpt :Also, according to the in vivo and in vitro electrophysiological studies, orexin A and orexin B have an essential role in spinal sensory transmission, respectively (Grudt et al., 2002; Peng et al., 2008). Based on a large body of literature on behavioral and pharmacological aspects of orexin A and B administration, supporting these electrophysiological evidences, it has been deduced that the intrathecal administration of orexin A and, to a lesser extent, orexin B inhibits withdrawal response and spontaneous nociceptive behavior in acute, inflammatory, chemical, neuropathic, and postsurgical models of pain (Bingham et al., 2001; Cheng et al., 2003; Jeong and Holden, 2009; Kajiyama et al., 2005; Mobarakeh et al., 2005a; Sakurai et al., 1998; Yamamoto et al., 2002, 2003). The anti-nociceptive actions of orexins was blocked via intrathecally administered SB-334867, once again exhibiting that pain modulation can be mediated through OX1 receptors (Gotter et al., 2012).