• Adrian Miranda, Shachar Peles, Reza Shaker, Colin Rudolph, and Jyoti N Sengupta.
• Division of Gastroenterology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA. amiranda@mail.mcw.edu
• J. Physiol. (Lond.). 2006 May 1;572(Pt 3):775-87.

AbstractThe role ofintramuscular, low pH saline injections during the neonatal period in the development and maintenance of visceral hyperalgesia has not been systematically studied. We aimed to investigate alterations in visceral sensation and neural circuitry that result from noxious stimuli in early life. Neonatal male Sprague-Dawley rats received sterile saline injections of pH 4.0 or 7.4 in the gastrocnemius muscle starting at postnatal day 8. Injections were given unilaterally every other day for 12 days ending on postnatal day 20. A third group received needle prick only on the same shedule as the second group, while a fourth group was left naïve. At 2 months of age, rats underwent assessment of cutaneous and deep somatic sensitivity using von Frey filaments and gastrocnemius muscle pinch, respectively. A visceromotor response (VMR) to graded colorectal distension (CRD; 10-80 mmHg for 30 s with 180 s interstimulus intervals) was recorded. Extracellular single-unit recordings from the thoracolumbar spinal neurons (T13-L1) were performed in adult pH 4.0 injected and naïve controls. There was no difference in the threshold for response to mechanical stimulation of the paw in rats injected with pH 4.0 saline compared to all other groups. Conversely, rats treated with pH 4.0 saline showed a significant bilateral reduction in withdrawal threshold to muscle pinch as adults (P < 0.05). At colorectal distensions > or = 20 mmHg, an increase in the VMR was observed in the pH 4.0 injected group compared to all other groups (P < 0.05). Spinal neurons were classified as short latency abrupt (SL-A) or short latency sustained (SL-S). Spontaneous firing of SL-S (20.6 +/- 2.2 impulses s(-1)), but not SL-A neurons (5.3 +/- 0.9 impulses s(-1)) in the pH 4.0 treated rats was significantly higher than in control rats (SL-S, 2.6 +/- 0.8 impulses s(-1); SL-A, 3.1 +/- 0.7 impulses s(-1)). The response of SL-S neurons to CRD in the pH 4.0 group was significantly higher at distension pressures > or = 20 mmHg. Nociceptive somatic stimulation in neonatal rats results in chronic deep somatic and visceral hyperalgesia in adulthood. Colorectal distension-sensitive SL-S neurons are primarily sensitized to neonatal somatic stimulation.

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