Intra-Periaqueductal Gray Matter Microinjection of Orexin-A Decreases Formalin-Induced Nociceptive Behaviors in Adult Male Rats

Zarmehri, Hassan Azhdari; Semnanian, Saeed; Fathollahi, Yaghoub; Erami, Elaheh; Khakpay, Roghaieh; Azizi, Hossein; Rohampour, Kambiz

doi:10.1016/j.jpain.2010.09.006

Cited by 58 publications

(23 citation statements)

References 25 publications

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“…The finding that intra-vlPAG microinjection of SB334867 reduced tail-flick latency in mice confirms the vlPAG as an important site of action for orexin-induced supraspinal antinociception (Ho et al, 2011;Azhdari-Zarmehri et al, 2011). In ob/ob mice, both the OX-A-mediated reduced-pain sensitivity and enhanced OFF-decreased ON cell activity were markedly reduced by treatment with AM251 at a dose inactive in wt mice, thus strongly suggesting that the CB 1 -mediated disinhibition produced by retrograde 2-AG after OX1-R receptor activation has a major role in OX-A-induced antinociception in the vlPAG.…”

Section: Discussionmentioning

confidence: 65%

Orexin-A and Endocannabinoid Activation of the Descending Antinociceptive Pathway Underlies Altered Pain Perception in Leptin Signaling Deficiency

Cristino

Luongo

Imperatore

et al. 2015

Neuropsychopharmacol

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Pain perception can become altered in individuals with eating disorders and obesity for reasons that have not been fully elucidated. We show that leptin deficiency in ob/ob mice, or leptin insensitivity in the arcuate nucleus of the hypothalamus in mice with high-fat diet (HFD)-induced obesity, are accompanied by elevated orexin-A (OX-A) levels and orexin receptor-1 (OX1-R)-dependent elevation of the levels of the endocannabinoid, 2-arachidonoylglycerol (2-AG), in the ventrolateral periaqueductal gray (vlPAG). In ob/ob mice, these alterations result in the following: (i) increased excitability of OX1-R-expressing vlPAG output neurons and subsequent increased OFF and decreased ON cell activity in the rostral ventromedial medulla, as assessed by patch clamp and in vivo electrophysiology; and (ii) analgesia, in both healthy and neuropathic mice. In HFD mice, instead, analgesia is only unmasked following leptin receptor antagonism. We propose that OX-A/endocannabinoid cross talk in the descending antinociceptive pathway might partly underlie increased pain thresholds in conditions associated with impaired leptin signaling.

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Section: Discussionmentioning

confidence: 65%

Orexin-A and Endocannabinoid Activation of the Descending Antinociceptive Pathway Underlies Altered Pain Perception in Leptin Signaling Deficiency

Cristino

Luongo

Imperatore

et al. 2015

Neuropsychopharmacol

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“…Recording of nociceptive behaviors started after formalin injection (0 min) and was continued for 90 min. Formalin-induced nociceptive behaviours were calculated and evaluated separately during the phase 1 (1–7 min), inter-phase (8–14 min), the phase 2A (15–60 min) and the phase 2B (61–90 min) (Abbott, et al, 1995; Azhdari-Zarmehri, et al, 2011). …”

Section: Methodsmentioning

confidence: 99%

Characterization of Nociceptive Behaviors Induced by Formalin in the Glabrous and Hairy Skin of Rats

Erami

Azhdari-Zarmehri

Imoto

et al. 2017

BCN

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Introduction:Glabrous skin and hairy skin are innervated by different types of noxious fibers. However, the different nociceptive behaviors induced by formalin, a commonly used model of acute inflammatory pain, have not yet been systematically examined in the glabrous and hairy skin.Methods:In this study, we compared nociceptive behaviors induced by formalin injections (2%, 4%, and 8%) into either glabrous skin (plantar surface) of the hind paw or hairy skin of the hind limb in adult rats.Results:A typical biphasic nociceptive response was seen after formalin injection into the plantar surface of the hind paw. A brief interphase separates the first and second phases where nociceptive behaviors were barely spotted. However, following subcutaneous injection into the hairy skin nociceptive behaviors were only seen after 10 minutes of formalin injection, which correlates in time with the second phase of the formalin response. First phase nociceptive behaviors were never seen with hairy skin injection, even following multiple injections of formalin.Conclusion:These data suggest that nociceptive behaviors and spinal responses induced by formalin injections to glabrous and hairy skin areas are different, and that the first and second phases may be mediated through different noxious afferent fibers.

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“…Neuropeptide Quantification It has been shown that neurotensin is implicated in analgesia via its actions within central and peripheral pain modulatory circuits, 23 oxytocin plays an antinociceptive role in the central nervous system, 2 and orexin is involved in nociceptive sensory processes. 3,24 Neuropeptides were determined by a Luminex (Luminex Corporation, Austin, TX) assay (Milliplex; EMD Millipore Corporation, Billerica, MA). This kit allows the simultaneous quantification of neurotensin, orexin A, and oxytocin (Milliplex HNP-35K; EMD Millipore Corporation).…”

Section: Outcome Measuresmentioning

confidence: 99%

“…61,68 Recent animal studies show that the analgesia produced by joint mobilization involves serotonin and noradrenaline receptors in the spinal cord, thereby performing a supporting role for central mechanisms of pain modulation. 60 Several neuropeptides, such as neurotensin, 23 oxytocin, 29 or orexin A, 3 have been associated with hypoalgesia and pain modulation, and it is well known that cortisol plays an analgesic role related to stress responses. 4,44 Recent theories have also suggested that chronic pain could be partly maintained by maladaptive physiological responses of the organism facing a recurrent stressor, a situation related to high cortisol levels.…”

mentioning

confidence: 99%

Changes in Biochemical Markers of Pain Perception and Stress Response After Spinal Manipulation

Plaza-Manzano

Molina²,

Lomas‐Vega³

et al. 2014

J Orthop Sports Phys Ther

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Intra-Periaqueductal Gray Matter Microinjection of Orexin-A Decreases Formalin-Induced Nociceptive Behaviors in Adult Male Rats

Cited by 58 publications

References 25 publications

Orexin-A and Endocannabinoid Activation of the Descending Antinociceptive Pathway Underlies Altered Pain Perception in Leptin Signaling Deficiency

Orexin-A and Endocannabinoid Activation of the Descending Antinociceptive Pathway Underlies Altered Pain Perception in Leptin Signaling Deficiency

Characterization of Nociceptive Behaviors Induced by Formalin in the Glabrous and Hairy Skin of Rats

Changes in Biochemical Markers of Pain Perception and Stress Response After Spinal Manipulation

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