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Received February 22, 2006
Revised February 24, 2006
Accepted after revision February 26, 2006
1 Medical College of Wisconsin
2 Medical College of WIsconsin
* To whom correspondence should be addressed. E-mail: amiranda{at}mail.mcw.edu.
The role of intramuscular, 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 pH 7.4 in the gastrocnemius muscle (GM) starting at postnatal day 8 (P8). Injections were given unilaterally every other day for 12 days ending on postnatal day 20 (P20). A third group received needle prick only, while a forth group was left naïve. At 2 months age rats underwent assessment of cutaneous and deep somatic sensitivity using von Frey filaments and GN muscle pinch, respectively. A visceromotor response (VMR) to graded colorectal distension (10-80mmHg, 30s, 180s inter-stimulus intervals) was recorded. Extracellular single-unit recordings from the thoraco-lumbar 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 when compared to all other groups. Conversely, rats treated with pH 4.0 showed a significant bilateral reduction in withdrawal threshold to muscle pinch as adults (p<0.05). At distensions
20mmHg, an increase in the VMR to CRD 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 or short latency sustained. Spontaneous firing of SL-S (20.6± 2.2 imp/s), but not SL-A (5.3 ± 0.9 imp/s) neurons in the pH 4.0 treated rats was significantly higher than control (SL-S: 2.6 ± 0.8, SL-A: 3.1 ± 0.7 imp/s). The response of SL-S neurons to CRD in the pH 4.0 group was significantly higher at distension pressures
20mmHg. Nociceptive somatic stimulation in neonatal rats results in chronic deep somatic and visceral hyperalgesia in adulthood. CRD-sensitive SL-S neurons are primarily sensitized to neonatal somatic stimulation.
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