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 IB4. Previous work suggested that neurons in the inner part of lamina II (IIi), onto which IB4-positive sensory neurons project, facilitate nociceptive transmission following tissue or nerve injury. Using an IB4-saporin conjugate (IB4-SAP), we examined the contribution of IB4-positive neurons to nociceptive processing in rats with and without nerve injury. Intrasciatic injection of IB4-SAP (5 mug/5 mul) significantly decreased IB4-labeling and immunoreactive P2X3 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 IB4-SAP-treated, but not control (saline or saporin only), rats. Acute NGF-induced hyperalgesia was also attenuated following IB4-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 IB4-SAP-treated animals whereas immunoreactive PKCgamma decreased 2, but not 4, weeks post-injury. Quantitative RT-PCR revealed a reduction in P2X3 mRNA in L4 DRG of IB4-SAP-treated animals, but no change in TrkA expression. Our results suggest that IB3-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. (C) 2004 Elsevier B.V. All rights reserved.