Bailey AL, Bennett G, Ribeiro-da-Silva A (2005) Selective ablation of non-peptidergic C-fibers using IB4-saporin as a tool to identify the functional role of these fibers in pain transmission. Neuroscience 2005 Abstracts 169.14. Society for Neuroscience, Washington, DC.
Summary: Non-peptidergic primary sensory afferents represent a sub-population of unmyelinated C-fibres implicated in the transmission of pain-related information. Evidence indicates that these afferents play a role in pain transmission distinct from peptidergic afferents. However, their exact function in pain signalling is unknown. Investigating alterations in pain behaviours and changes in neurotransmitter and receptor expression in the absence of these sensory afferents may provide some insight into their relative importance in acute and chronic pain conditions. We therefore examined the functional consequences of the selective ablation of non-peptidergic fibres in numerous models of acute pain using Isolectin B4 conjugated to saporin (IB4-SAP). Unilateral injection of IB4-SAP into the sciatic nerve resulted in the selective ablation of IB4-positive neurons in the ipsilateral dorsal root ganglion (DRG). Examination of the central terminals of non-peptidergic primary afferents in the dorsal horn revealed the near complete loss of IB4-positive, P2X3 immunoreactive (IR) varicosities. Moreover, there were marked decreases in TRPV1-IR and substance P (SP-IR) with no change in calcitonin-gene-related peptide (CGRP). Examination of a marker of inhibitory interneurons revealed no changes in GAD-IR. Behavioural analysis showed that IB4-SAP treatment had no effect on acute thermal sensitivity, acute mechanical or cold sensitivity. In an animal model of acute inflammation, IB4-SAP treatment had no effect on inflammatory heat hyperalgesia or mechanical allodynia. However, animals treated with IB4-SAP showed attenuated heat hyperalgesia induced by capsaicin 30 and 60 minutes post-injection. Data relative to acute nociceptive thresholds after other chemical stimuli will be presented. These data indicate that non-peptidergic fibres are minimally involved in acute and inflammatory pain, and may play a more prominent role in high threshold thermal sensation.
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