Skin incision-induced receptive field responses of mechanosensitive peripheral neurons are developmentally regulated in the rat

Abstract

Maturation of the nervous system results in changes in both central and peripheral processing. To better understand responses to injury in the young, developmental differences in the acute response to incision were investigated in both tactile and nociceptive myelinated peripheral mechanosensitive afferent neurons in vivo. Neuronal intrasomal recordings were performed in juvenile and infant rats in 34 L5 dorsal root ganglia, and each neuron was phenotypically defined. Neurons had a mechanosensitive receptive field in the glabrous skin on the plantar surface of the hind paw, which was characterized at baseline and for up to 45 min after incision. Fundamental maturational differences in the effect of incision were clear: in high-threshold nociceptive mechanoreceptors, the mechanical threshold decreased immediately and the receptive field size increased rapidly in juvenile rats but not in infant rats. Additionally, a divergence in changes in the instantaneous response frequency of tactile afferents occurred between the two ages. These differences may help explain maturational differences in responses to peripheral injury and suggest that differences in central nervous system responses may be partially mitigated by spatially confined and frequency-dependent differences resulting from tactile and nociceptive mechanosensitive input.

Fig. 1.

A: schematic diagram of the in vivo rat L5 preparation (lateral view). Colored areas delineate approximate dermatome boundaries where skin sensory neuron receptive fields (RF) were located. B: paw diagram (left) and photograph (right) showing the foot position.

Fig. 2.

Distribution of cellular subtypes (nociceptive and tactile) based on conduction velocity (CV) and action potential (AP) duration. The graph shows log₁₀(CV) versus log₁₀(AP duration) at the 50% of AP amplitude (D₅₀) in both juvenile and infant rats. These two neuronal electrical characteristics of neuronal activation are principal components of neuronal classification. The CV was faster and the D₅₀ was shorter in tactile [low-threshold mechanoceptor (LTMR)] nerve fibers than in nociceptive [Aδ-range high-threshold mechanoreceptor (AHTMR)] neurons at both ages, whereas the CV was faster for both nerve fibers in older animals. P7, postnatal day 7 (infant animals); P28, postnatal day 28 (juvenile animals).

Fig. 3.

Effect of injury on the mechanical threshold of nociceptive (A) and non-nociceptive (B) afferents after injury in both juvenile and infant rats. Open bars show before incision; shaded bars show after incision. Data are medians, with boxes representing the 25th and 75th percentiles and whiskers representing ranges. Only nociceptive (AHTMR) neurons in juvenile animals were acutely affected by incision. Significance level: *P < 0.01.

Fig. 4.

RF size change after incision for tactile (A) and nociceptive (B) neurons. After incision, the RF size increased more than 10 times the initial size in juvenile animals in nociceptive (AHTMR) neurons but not in tactile (LTMR) neurons. No change in the RF size was seen in infant animals in response to incision. Significance level: ***P < 0.01.

Fig. 5.

A: schematic diagram of temporal RF changes after injury on two nociceptors (a and b) recorded in the glabrous skin (paw) of a juvenile rat. The straight line shows the extent and location of the incision. The numbers beside a or b represent the order in which high-sensibility areas (HSAs) emerged (0, initial RF; gray) and their relative areas of sensibility (1, 2, or 3 RFs, white), with the center noted with a dot where the threshold was established. Also, the final RF size after 20 min is shown (the entire large circular area). B: absolute values of each HSA mechanical threshold measure every 5 min after the incision. Note that the b₂ value was lower than the value reached at b₀. C: electrical response elicited by the application of suprathreshold mechanical force on the initial cellular RF 10 min after the incision. Scale bars = 2 s, 40 mV.

Fig. 6.

Instantaneous response frequency (IRF) of tactile and nociceptive neurons to threshold mechanical force in juvenile (A) and infant (B) animals. The IRF for both tactile (LTMR) and nociceptive (AHTMR) neurons was not different between ages. However, whereas there was a significant increase in IRF for AHTMR neurons at both ages, there was a significant increase in IRF for infant animals and a significant decrease in IRF for juvenile animals. △, tactile neurons (LTMRs); ●, nociceptors (AHTMRs).