title: Descending facilitatory influences from the rostral medial medulla mediate secondary, but not primary hyperalgesia in the rat.
abstract: Prolonged nociceptive input following peripheral injury results in hyperalgesia (enhanced response to a noxious stimulus), which is thought to occur as a consequence of sensitization of primary afferent nociceptors and enhanced excitability of spinal dorsal horn nociceptive neurons (central sensitization). Since there is often an expansion of hyperalgesia to tissue adjacent, and even distant from the site of injury (secondary hyperalgesia), it is thought that this phenomenon primarily involves mechanisms of central modulation/plasticity. In contrast, hyperalgesia observed at the site of tissue injury (primary hyperalgesia) involves peripheral mechanisms. In the current study, we examined the relative contribution of descending nociceptive facilitatory systems from the rostral medial medulla to enhanced behavioral nociceptive responses in models of primary and secondary hyperalgesia in awake rats. The effect of bilateral rostral medial medulla lesions produced by the soma-selective neurotoxin ibotenic acid was determined in three different models of cutaneous thermal hyperalgesia following peripheral inflammation: (i) intraplantar injection of carrageenan into the hindpaw (model of primary hyperalgesia); (ii) intra-articular injection of carrageenan/kaolin into the knee of the hind leg (model of secondary hyperalgesia); and (iii) topical application of mustard oil to the hind leg (model of secondary hyperalgesia). Compared with sham lesion animals, a bilateral lesion of the rostral medial medulla completely blocked thermal hyperalgesia in the two models of secondary hyperalgesia (intra-articular carrageenan/kaolin injection into the knee and topical mustard oil application to the hind leg), but was ineffective in blocking facilitation of the thermal paw withdrawal response in the model of primary hyperalgesia (intraplantar carrageenan injection into the hindpaw). These results suggest that primary and secondary hyperalgesia are differentially modulated in the CNS, and support the notion that descending nociceptive facilitatory influences from the rostral medial medulla significantly contribute to secondary, but not primary, hyperalgesia.
authors.affiliation: Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City 52242, USA.
authors.forename: M O
authors.initials: MO
authors.lastname: Urban
authors.forename: P K
authors.initials: PK
authors.lastname: Zahn
authors.forename: G F
authors.initials: GF
authors.lastname: Gebhart
mesh_terms: D000818:Animals; D002351:Carrageenan / Q000633:toxicity; D007839:Functional Laterality; D006614:Hindlimb; D006358:Hot Temperature; D006930:Hyperalgesia / Q000473:pathology / Q000503:physiopathology*; D007051:Ibotenic Acid / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008845:Microinjections; D009149:Mustard Plant; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity; D010146:Pain / Q000473:pathology / Q000503:physiopathology*; D010936:Plant Extracts / Q000633:toxicity; D010938:Plant Oils; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*
chemical_list: D009498:Neurotoxins; D010936:Plant Extracts; D010938:Plant Oils; D007051:Ibotenic Acid; D002351:Carrageenan; C027793:mustard oil