title: Biochemical and pharmacological assessment of MAP-kinase signaling along pain pathways in experimental rodent models: a potential tool for the discovery of novel antinociceptive therapeutics.
abstract: Injury to the peripheral or central nervous system can induce changes within the nervous tissues that promote a state of sensitization that may underlie conditions of pathological chronic pain. A key biochemical event in the initiation and maintenance of peripheral and central neuronal sensitization associated with chronic pain is the phosphorylation and subsequent activation of mitogen-activated protein kinases (MAPKs) and immediate early gene transcription factors, in particular cAMP-response element binding protein (CREB). In this commentary we review the preclinical data that describe anatomical and mechanistic aspects of nociceptive-induced signaling along nociceptive pathways including peripheral cutaneous axons, the dorsal root ganglia, spinal cord dorsal horn and cerebral cortex. In addition to the regional manifestation of nociceptive signaling, investigations have attempted to elucidate the cellular origin of biochemical nociceptive processing in which communication, i.e. cross-talk between neurons and glia is viewed as an essential component of pathogenic pain development. Here, we outline a research strategy by which nociceptive-induced cellular signaling in experimental pain models, specifically MAPK and CREB phosphorylation can be utilized to provide mechanistic insight into drug-target interaction along the nociceptive pathways. We describe a series of studies using nociceptive inflammatory and neuropathic pain models to investigate the effects of known pain therapeutics on nociceptive-induced biochemical signaling and present this as a complementary research strategy for assessing antinociceptive activity useful in the preclinical development of novel pain therapeutics.
authors.affiliation: AbbVie Inc., Neuroscience Discovery, North Chicago, IL, USA.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Edelmayer
authors.affiliation: AbbVie Inc., Neuroscience Discovery, North Chicago, IL, USA.
authors.forename: Jill-Desiree
authors.initials: JD
authors.lastname: Brederson
authors.affiliation: AbbVie Inc., Neuroscience Discovery, North Chicago, IL, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Jarvis
authors.affiliation: AbbVie Inc., Neuroscience Discovery, North Chicago, IL, USA. Electronic address: robert.s.bitner@abbvie.com.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Bitner
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D059350:Chronic Pain / Q000188:drug therapy / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology*; D059225:Nociception / Q000187:drug effects*
chemical_list: D000700:Analgesics
keywords: Chronic pain; Dorsal root ganglion; Mitogen-activated protein kinases; Neuronal sensitization; Spinal cord