Transgenic mice possessing increased numbers of nociceptors do not exhibit increased behavioral sensitivity in models of inflammatory and neuropathic pain

Abstract

At least two classes of nociceptors can be distinguished based on their growth factor requirements: glial cell-line derived neurotrophic factor (GDNF)- and nerve growth factor (NGF)-dependent primary afferent neurons. Based on numerous anatomical and biochemical differences, GDNF- and NGF-dependent neurons have been proposed to be involved in the development of different types of persistent pain. To examine this hypothesis we used two lines of transgenic mice that contained a supernormal number of either NGF- or GDNF-dependent neurons (referred to as NGF-OE and GDNF-OE mice, respectively). These mice were tested in a model of inflammatory pain (induced by injection of complete Freund's adjuvant) and neuropathic pain (using a spinal nerve ligation protocol). Contrary to expectations, neither line of transgenic mice became more hyperalgesic following induction of persistent pain. In fact, NGF-OE mice recovered more rapidly and became hypoalgesic despite extensive paw swelling in the inflammatory pain model. In the neuropathic pain model, only wildtype mice became hyperalgesic. Real-time PCR analysis showed that the NGF-OE and GDNF-OE mice exhibited changes in neuronal-specific mRNAs in the dorsal root ganglia but not the spinal cord dorsal horn. These results indicate that increasing the number of nociceptors results in potent compensatory mechanisms that may begin with changes in the sensory neurons themselves.