title: Pain from intra-articular NGF or joint injury in the rat requires contributions from peptidergic joint afferents.
abstract: Non-physiological stretch of the cervical facet joint's capsular ligament induces persistent behavioral hypersensitivity and spinal neuronal hyperexcitability via an intra-articular NGF-dependent mechanism. Although that ligament is innervated by nociceptors, it is unknown if a subpopulation is exclusively responsible for the behavioral and spinal neuronal responses to intra-articular NGF and/or facet joint injury. This study ablated joint afferents using the neurotoxin saporin targeted to neurons involved in either peptidergic ([Sar(9),Met (O2)(11)]-substance P-saporin (SSP-Sap)) or non-peptidergic (isolectin B4-saporin (IB4-Sap)) signaling to investigate the contributions of those neuronal populations to facet-mediated pain. SSP-Sap, but not IB4-Sap, injected into the bilateral C6/C7 facet joints 14 days prior to an intra- articular NGF injection prevents NGF-induced mechanical and thermal hypersensitivity in the forepaws. Similarly, only SSP- Sap prevents the increase in mechanical forepaw stimulation- induced firing of spinal neurons after intra-articular NGF. In addition, intra-articular SSP-Sap prevents both behavioral hypersensitivity and upregulation of NGF in the dorsal root ganglion after a facet joint distraction that normally induces pain. These findings collectively suggest that disruption of peptidergic signaling within the joint may be a potential treatment for facet pain, as well as other painful joint conditions associated with elevated NGF, such as osteoarthritis.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Kras
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Weisshaar
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Parul S
authors.initials: PS
authors.lastname: Pall
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: winkelst@seas.upenn.edu.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Winkelstein
mesh_terms: D000200:Action Potentials; D000818:Animals; D001522:Behavior, Animal; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology; D037102:Lectins / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D020932:Nerve Growth Factor / Q000009:adverse effects / Q000378:metabolism* / Q000494:pharmacology; D009475:Neurons, Afferent / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D017288:Pain Threshold; D010812:Physical Stimulation; D017207:Rats, Sprague-Dawley; D054789:Ribosome Inactivating Proteins, Type 1 / Q000378:metabolism / Q000494:pharmacology; D000076985:Saporins; D015398:Signal Transduction; D066148:Spinal Cord Dorsal Horn / Q000503:physiopathology; D013373:Substance P / Q000378:metabolism; D021801:Zygapophyseal Joint / Q000187:drug effects* / Q000293:injuries* / Q000503:physiopathology
chemical_list: C496198:IB4-saporin conjugate; D037102:Lectins; D009479:Neuropeptides; D054789:Ribosome Inactivating Proteins, Type 1; D013373:Substance P; D020932:Nerve Growth Factor; D000076985:Saporins
keywords: Afferent; Facet joint; NGF; Neuronal hyperexcitability; Pain; Trauma