The behavioral and neuroanatomical effects of IB4-saporin treatment in rat models of nociceptive and neuropathic pain.
One distinguishing feature of primary afferent neurons is their ability to bind the lectin IB(4). Previous work suggested that neurons in the inner part of lamina II (IIi), onto which IB(4)-positive sensory neurons project, facilitate nociceptive transmission following tissue or nerve injury. Using an IB(4)-saporin conjugate (IB(4)-SAP), we examined the contribution of IB(4)-positive neurons to nociceptive processing in rats with and without nerve injury. Intrasciatic injection of IB(4)-SAP (5 mug/5 mul) significantly decreased IB(4)-labeling and immunoreactive P(2)X(3) in the spinal cord and delayed the behavioral and neuroanatomical consequences of L5 spinal nerve ligation (SNL) injury. In the absence of injury, thermal and mechanical nociceptive thresholds increased 2 weeks post-treatment only in IB(4)-SAP-treated, but not control (saline or saporin only), rats. Acute NGF-induced hyperalgesia was also attenuated following IB(4)-SAP treatment. In the SNL model, mechanical allodynia failed to develop 1 and 2 weeks post-injury, but was fully established by 4 weeks. Moreover, neuropeptide Y immunoreactivity (NPY-ir), which increases in the spinal cord after nerve injury, was unchanged in IB(4)-SAP-treated animals whereas immunoreactive PKCgamma decreased 2, but not 4, weeks post-injury. Quantitative RT-PCR revealed a reduction in P(2)X(3) mRNA in L4 DRG of IB(4)-SAP-treated animals, but no change in TrkA expression. Our results suggest that IB(4)-positive neurons in L4 are required for the full expression of NGF-induced hyperalgesia and participate in the behavioral and anatomical consequences that follow injury to the L5 spinal nerve.
Tarpley
Jason W
JW
Department of Pharmacology, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA.
Kohler
Martin G
MG
Martin
William J
WJ
D000818:Animals; D003603:Cytotoxins / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000473:pathology / Q000503:physiopathology; D037102:Lectins / Q000378:metabolism* / Q000494:pharmacology; D008026:Ligation; D008161:Lumbosacral Region; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced*; D009437:Neuralgia / Q000473:pathology / Q000503:physiopathology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000473:pathology*; D009619:Nociceptors / Q000187:drug effects / Q000473:pathology*; D010146:Pain / Q000473:pathology / Q000503:physiopathology*; D017288:Pain Threshold; D010523:Peripheral Nervous System Diseases / Q000473:pathology / Q000503:physiopathology*; D037121:Plant Lectins; D051381:Rats; D017207:Rats, Sprague-Dawley; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013127:Spinal Nerves / Q000293:injuries / Q000473:pathology / Q000503:physiopathology
D003603:Cytotoxins; C045475:Griffonia simplicifolia lectins; C496198:IB4-saporin conjugate; D037102:Lectins; D037121:Plant Lectins; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins