Rat model of cancer-induced bone pain

INTRODUCTION: Clinical data on cancer-induced bone pain (CIBP) suggest extensive changes in sensory function. In a previous investigation of an animal model of CIBP, we have observed that changes in intrinsic membrane properties and excitability of dorsal root ganglion (DRG) nociceptive neurons correspond to mechanical allodynia and hyperalgesia. OBJECTIVES: To investigate the mechanisms underlying changes in nonnociceptive sensory neurons in this model, we have compared the electrophysiological properties of primary nonnociceptive sensory neurons at <1 and >2 weeks after CIBP model induction with properties in sham control animals. METHODS: Copenhagen rats were injected with 10⁶ MAT-LyLu rat prostate cancer cells into the distal femur epiphysis to generate a model of CIBP. After von Frey tactile measurement of mechanical withdrawal thresholds, the animals were prepared for acute electrophysiological recordings of mechanically sensitive neurons in the DRG in vivo. RESULTS: The mechanical withdrawal threshold progressively decreased in CIBP model rats. At <1 week after model induction, there were no changes observed in nonnociceptive Aβ-fiber DRG neurons between CIBP model rats and sham rats. However, at >2 weeks, the Aβ-fiber low-threshold mechanoreceptors (LTMs) in CIBP model rats exhibited a slowing of the dynamics of action potential (AP) genesis, including wider AP duration and lower AP amplitude compared with sham rats. Furthermore, enhanced excitability of Aβ-fiber LTM neurons was observed as an excitatory discharge in response to intracellular injection of depolarizing current into the soma. CONCLUSION: After induction of the CIBP model, Aβ-fiber LTMs at >2 weeks but not <1 week had undergone changes in electrophysiological properties. Importantly, changes observed are consistent with observations in models of peripheral neuropathy. Thus, Aβ-fiber nonnociceptive primary sensory neurons might be involved in the peripheral sensitization and tumor-induced tactile hypersensitivity in CIBP.