The journal of pain : official journal of the American Pain Society
-
Neonatal peripheral inflammatory insult might result in the alteration of neuronal development in the nociceptive circuit. During early postnatal period, neurotrophins play important roles in neural development and sensory nerve innervation in the central and peripheral nervous systems. In this study, we investigated mRNA expression for neurotrophic factors and their receptors in the dorsal root ganglia of rat pups during postnatal life after peripheral inflammation induced by injection of complete Freund's adjuvant (CFA) into hind paw on postnatal day 1. Our results showed that mRNA expression levels of alpha-calcitonin gene-related peptides, tropomyosin-related kinase-A (trkA), p75 neurotrophin receptor (p75(NTR)), and brain-derived neurotrophic factor (BDNF) elevated significantly after CFA treatment. Such an increase began 1 day after CFA treatment and lasted 2 to 3 days for trkA, p75(NTR), and BDNF. In contrast, there was no change in mRNA expression levels for neurotrophin-4/5, beta-nerve growth factor (beta-NGF), trkB, glial cell line-derived neurotrophin factor, and receptor protein tyrosine kinase protein. Our study demonstrated that neonatal peripheral inflammatory insult might result in molecular changes of neurotrophic factors, particularly in NGF receptors and BDNF, in the process of neuronal development and plasticity in primary afferents during early neonatal period. ⋯ Neonatal peripheral inflammation model has been used for the exploration of neuropathic pain mechanism for years. This work provided further detailed information about possible neurotransmitters and peptides involved in this process. This might also lead to future clinical application.
-
It is not known if a cytokine cascade develops during muscle inflammation and whether cytokines contribute to muscle inflammatory pain. We measured plasma and tissue cytokine concentrations, and behavioral responses to noxious mechanical stimuli, after inducing inflammation in the gastrocnemius muscle and the hind paw of rats. Tissue and plasma samples were taken 3, 6, or 24 h after carrageenan or saline injection into one of the 2 sites. Tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and cytokine-induced neutrophil chemoattractant 1 (CINC-1) concentrations were measured. Hyperalgesia was present 3 h after carrageenan injection into the hind paw and muscle. The TNF-alpha was elevated significantly in the inflamed hind paw tissue (P < .001) but not in inflamed muscle tissue. IL-1beta was elevated 6 h after carrageenan injection in the hind paw tissue but only 24 h in the muscle tissue (P < .001). The IL-6 was elevated 3 h after injection in the hind paw tissue but only after 6 h in the muscle tissue (P < .01). The CINC-1 in plasma, muscle, and hind paw was elevated from 3 h to 24 h after carrageenan injection (P < .01). The release of IL-1beta and IL-6, known to mediate hyperalgesia elsewhere, is delayed in muscle inflammation compared with cutaneous inflammation, whereas TNF-alpha is not elevated during muscle inflammation. ⋯ The quality and mechanisms of muscle pain are different from that of cutaneous pain. So too is the pattern of cytokine release during inflammation. Inhibiting TNF-alpha is unlikely to be effective in managing inflammatory muscle pain, but other cytokines, notably IL-1beta and CINC-1, may prove useful therapeutic targets.