Isolectin B4-Positive and -Negative Nociceptors Are Functionally Distinct

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Abstract
Small-diameter sensory neurons that are primarily nociceptors can be divided neurochemically into two populations: isolectin B4(IB4)-positive nonpeptidergic neurons, and IB4-negative peptidergic neurons. It has been shown that IB4-positive neurons depend on glial-derived neurotrophic factor (GDNF), whereas IB4-negative neurons depend on NGF for survival during postnatal development (Molliver et al., 1997). Furthermore, these two populations of nociceptors terminate in distinct regions of the superficial spinal cord. To date, however, no evidence exists that indicates whether these two groups of nociceptors have distinct functional roles in the process of nociception (Snider and McMahon, 1998). To search for functional differences, we performed whole-cell voltage and current-clamp recordings on acutely isolated adult mouse dorsal root ganglion neurons that were labeled with fluorescent IB4. We found that IB4-positive neurons have longer-duration action potentials, higher densities of TTX-resistant sodium currents, and smaller noxious heat-activated currents than IB4-negative neurons. Furthermore, we show that NGF, but not GDNF, directly increases the number of neurons that respond to noxious heat. The different electrophysiological properties expressed by IB4-positive and -negative small neurons, including their different heat sensitivities, indicates that they may relay distinct aspects of noxious stimuli both acutely and after injuryin vivo.