Suckling and sucrose ingestion suppress persistent hyperalgesia and spinal Fos expression after forepaw inflammation in infant rats

Abstract

Sweet taste and nonnutritive suckling produce analgesia to transient noxious stimuli in infant rats and humans. The present study evaluated the pain-modulating effects of sucrose and suckling in a rat model of persistent pain and hyperalgesia that mimics the response to tissue injury in humans. Fore- and hindpaw withdrawal latencies from a 30 degrees or 48 degrees C brass stylus were determined in 10-day-old rats following paw inflammation induced by complete Freund's adjuvant (CFA; 1:1 injected s.c. in a 0.01 ml volume). CFA markedly decreased escape latencies to both 48 degrees and 30 degrees C stimulation, thereby demonstrating thermal hyperalgesia and mechanical allodynia. The combination of nonnutritive suckling and sucrose (7.5%, 0.01-0.06 ml/min) infusion markedly increased escape latencies to forepaw stimulation in both CFA-treated and control rats. In contrast, intraoral sucrose and suckling did not increase hindpaw withdrawal latencies in either control or CFA-inflamed rats. The effect was specific to sweet taste because neither water nor isotonic saline infusion affected forepaw escape latencies. Parallel findings were obtained for CFA-induced Fos-like immunoreactivity (Fos-LI), a marker of neuronal activation. Fos-LI was selectively induced in cervical and lumbar regions ipsilateral to forepaw and hindpaw inflammation, respectively. Suckling-sucrose treatment significantly reduced Fos-LI at the cervical but not at the lumbar regions. These findings demonstrate: (i) the development of persistent pain and hyperalgesia in 10-day-old rats that can be attenuated by endogenous pain-modulating systems activated by taste and nonnutritive suckling; (ii) the mediation of the sucrose-suckling analgesia and antihyperalgesia at the spinal level; and (iii) a differential rostrocaudal maturation of descending pain-modulating systems to the spinal cord of 10-day-old rats. These findings may provide new clinical approaches for engaging endogenous analgesic mechanisms in infants following tissue injury and inflammation.

Figure 1

(A) Effects of suckling and intraoral sucrose on paw withdrawal latencies of naive 10-day-old rats. (B) Baseline paw withdrawal responses and CFA-induced hyperalgesia. The numbers in the bars indicate the number of rats in each group. All rats had an intraoral cannula. (C) Effects of suckling and intraoral sucrose on paw withdrawal latencies of forepaw-inflamed newborns. Note scale difference. Asterisks indicate significant differences from relevant control groups (open bars). ∗, P < 0.05; ∗∗, P < 0.01; ∗∗∗, P < 0.001. Comparisons of filled bars for forepaw groups in C with open bars in A and B reveal that suckling-sucrose fully reversed the behavioral effects of CFA.

Figure 2

Photomicrographs illustrating the effects of intraoral sucrose and suckling on CFA-induced Fos-LI in the cervical (C7, A and B) and lumbar (L4, C and D) spinal cord of 10-day-old rats. The spinal dorsal horn ipsilateral to inflammation is shown with dorsum on top. (A and C) CFA-induced Fos-LI without intraoral sucrose and suckling. (B and D) CFA-induced Fos-LI with intraoral sucrose and suckling. (Bar = 0.1 mm.)

Figure 3

The effects of intraoral sucrose and suckling on the number of Fos-immunoreactive neurons in the cervical (C7-8) and lumbar (L4-5) spinal cord dorsal horn ipsilateral to forepaw (Upper) or hindpaw (Lower) inflammation. The mean numbers of Fos-labeled neurons from superficial (laminae I/II), deep (laminae V/VI), and whole dorsal horn are shown. The open bars show rats with inflammation only, and the filled bars show rats receiving sucrose and suckling after inflammation. Asterisks indicate significant differences between the two groups. ∗, P < 0.05.