A NEW MODEL OF VISCERAL HYPERALGESIA IN NEONATAL RATS: 197

Introduction: During development, the spinal cord is vulnerable to permanent structural and functional alterations in pain pathways. We aimed to investigate alterations in visceral sensation that result from noxious somatic stimulation during the neonatal period. We hypothesized that spinal neurons undergo permanent sensitization in areas of viscero-somatic convergence and that this sensitization can be attenuated by amitriptyline. Methods: Neonatal Sprague-Dawley rats received saline injections (0.1 ml) of pH 4.0 or pH 7.4 in the gastrocnemius muscle on alternate days (total 6). A third group received needle prick only, while a forth group was left naive (n = 10 per group). A stimulus response function to graded colorectal distension (CRD) (10-80 mmHg) was recorded at age 8-12 weeks. Extracellular single-unit recordings from spinal neurons (L1-L4) were performed in adult pH 4.0 injected rats and compared to naive controls. Neurons were sub-classified as short latency abrupt (SL-A, n = 24) or short latency sustained (SL-S, n = 23). The spontaneous activity and response to graded CRD was recorded for each neuron. Recordings were repeated following administration of amitriptyline (6 μmol/kg, i.v.). Results: Rats that received pH 4.0 injections as neonates developed visceral hyperalgesia with a significant increase in the visceromotor response (CRD ≥20 mmHg, p < 0.05). The spontaneous firing of SL-S (20.6 ± 4.5 imp/s), but not SL-A (6.4 ± 5.4 imp/s) neurons in the pH 4.0 group was higher than control (1.8 ± 0.1 and 4.3 ± 2.3 imp/s, respectively, p < 0.01). The responses of SL-S neurons to CRD in the pH 4.0 group were also higher at all distension pressures (p < 0.01). SL-A neurons did not differ from controls. Amitriptyline significantly decreased the spontaneous activity of sensitized SL-S neurons (17.6279 ± 1.9 vs 5.96 ± 2.0, p < 0.01) and the response to CRD at all pressures (p < 0.02) but had no effect on SL-A neurons. Conclusion: Nociceptive somatic stimulation in neonatal rats results in chronic visceral hyperalgesia. Sensitization occurs through sustained spinal neurons that can be modulated by amitriptyline.