|Title||Activation of descending pain-facilitatory pathways from the rostral ventromedial medulla by cholecystokinin elicits release of prostaglandin-E₂ in the spinal cord.|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Marshall TM, Herman DS, Largent-Milnes TM, Badghisi H, Zuber K, Holt SC, Lai J, Porreca F, Vanderah TW|
|Date Published||2012 Jan|
|Keywords||Animals, Cholecystokinin, Dinoprostone, Hyperalgesia, Male, Medulla Oblongata, Pain, Pain Measurement, Rats, Rats, Sprague-Dawley, Spinal Cord, Spinal Nerves|
Cholecystokinin (CCK) has been suggested to be both pro-nociceptive and "anti-opioid" by actions on pain-modulatory cells within the rostral ventromedial medulla (RVM). One consequence of activation of RVM CCK₂ receptors may be enhanced spinal nociceptive transmission; but how this might occur, especially in states of pathological pain, is unknown. Here, in vivo microdialysis was used to demonstrate that levels of RVM CCK increased by approximately 2-fold after ligation of L₅/L₆ spinal nerves (SNL). Microinjection of CCK into the RVM of naïve rats elicited hypersensitivity to tactile stimulation of the hindpaw. In addition, RVM CCK elicited a time-related increase in (prostaglandin-E₂) PGE₂ measured in cerebrospinal fluid from the lumbar spinal cord. The peak increase in spinal PGE₂ was approximately 5-fold and was observed at approximately 80 minutes post-RVM CCK, a time coincident with maximal RVM CCK-induced mechanical hypersensitivity. Spinal administration of naproxen, a nonselective COX-inhibitor, significantly attenuated RVM CCK-induced hindpaw tactile hypersensitivity. RVM-CCK also resulted in a 2-fold increase in spinal 5-hydroxyindoleacetic acid (5-HIAA), a 5-hydoxytryptophan (5-HT) metabolite, as compared with controls, and mechanical hypersensitivity that was attenuated by spinal application of ondansetron, a 5-HT₃ antagonist. The present studies suggest that chronic nerve injury can result in activation of descending facilitatory mechanisms that may promote hyperalgesia via ultimate release of PGE₂ and 5-HT in the spinal cord.
|PubMed Central ID||PMC3245767|
|Grant List||K02 DA018717 / DA / NIDA NIH HHS / United States |
K02 DA018717-05 / DA / NIDA NIH HHS / United States
R01 DA015205 / DA / NIDA NIH HHS / United States
R01 DA015205-05 / DA / NIDA NIH HHS / United States
R01-DA15205-01 / DA / NIDA NIH HHS / United States
Activation of descending pain-facilitatory pathways from the rostral ventromedial medulla by cholecystokinin elicits release of prostaglandin-E₂ in the spinal cord.
Faculty Member Reference:
Josephine Lai , Ph.D.
Tally Largent-Milnes, PhD
Frank Porreca, Ph.D.
Todd Vanderah, Ph.D.