Changes in functional properties of A-type but not C-type sensory neurons in vivo in a rat model of peripheral neuropathy

Abstract

Background: The aim of this study was to compare primary sensory neurons in controls and in an animal neuropathic pain model in order to understand which types of neurons undergo changes associated with peripheral neuropathy. On the basis of intracellular recordings in vivo from somata, L4 sensory dorsal root ganglion neurons were categorized according to action potential configuration, conduction velocity, and receptive field properties to mechanical stimuli.

Methods: Intracellular recordings were made from functionally identified dorsal root ganglion neurons in vivo in the Mosconi and Kruger animal model of peripheral neuropathic pain.

Results: In this peripheral neuropathy model, a specific population of Aβ-fiber low threshold mechanoreceptor neurons, which respond normally to innocuous mechanical stimuli, exhibited differences in action potential configuration and conduction velocity when compared with control animals. No abnormal conduction velocity, action potential shapes, or tactile sensitivity of C-fiber neurons were encountered.

Conclusion: This study provides evidence for defining a potential role of Aβ-fiber low threshold mechanoreceptor neurons that might contribute to peripheral neuropathic pain.

Keywords: action potential configuration; animal model; dorsal root ganglion; in vivo recording; neuropathic pain; peripheral neuropathy; primary sensory neuron.

Figure 1

Examples of APs recorded from mechanoreceptive neurons. (A) Representative intracellular somatic action potential of an A-fiber neuron evoked by electrical stimulation of the dorsal root showing the electrophysiological parameters measured, including: 1, resting membrane potential; 2, action potential duration at base; 3, action potential rise time; 4, action potential fall time; 5, action potential amplitude; 6, AHP duration to 50% recovery; 7, and afterhyperpolarization amplitude below Vm. In addition, maximum rising and falling rates, (dV/dt) max, were measured from the differential trace of the action potential. (B) Somatic action potentials evoked by dorsal root stimulation and recorded intracellularly from 12 mechanoreceptive neurons selected to represent the mean action potential duration values for each of the different groups of neurons in control (upper) and neuropathic (lower) animals. The action potential duration and conduction velocity for each neuron are given below each record. The horizontal lines across the action potentials indicate zero membrane potential. Abbreviations: HTM, high threshold mechanoreceptive neurons; LTM, low threshold mechanoreceptive neurons.

Figure 2

Comparison of action potential resting membrane potential and amplitude of dorsal root ganglion neurons between control and neuropathic rats. Scatter plots show the distribution of the variables with the median (horizontal line) superimposed in each case. Notes: Asterisks above the graph indicate the significant differences between control and neuropathic animals: *P < 0.05; **P < 0.01; ***P < 0.001. The absence of an asterisk indicates lack of a statistically significant difference. Abbreviations: HTM, high threshold mechanoreceptor neurons; LTM, low threshold mechanoreceptor neurons; UN, unresponsive neurons; CUT, Aβ LTM including guard/field hair neurons, rapidly adapting neurons and slowly adapting neurons; MS, Aβ LTM muscle spindle neurons.

Figure 3

Comparison of action potential dynamic parameters of dorsal root ganglion neurons between control and neuropathic rats. Scatter plots show the distribution of the variables with the median (horizontal line) superimposed in each case. Notes: Asterisks above the graph indicate the significant differences between control and neuropathic animals: *P < 0.05, **P < 0.01; ***P < 0.001. The absence of an asterisk indicates the lack of a statistically significant difference. Abbreviations: APdB, action potential duration at base; APRT, action potential rise time; APFT, action potential fall time; MRR, maximum AP rising rate; MFR, maximum AP falling rate; HTM, high threshold mechanoreceptor neurons; LTM, low threshold mechanoreceptor neurons; UN, unresponsive neurons.

Figure 4

Comparison of AHP variables of DRG neurons between control and neuropathic rats. Scatter plots show the distribution of the variables with the median (horizontal line) superimposed in each case. Notes: Asterisks above the graph indicate significant differences between control and neuropathic animals: *P < 0.05, **P < 0.01; ***P < 0.001. The absence of an asterisk indicates the lack of a statistically significant difference. Abbreviations: AHPA, afterhyperpolarization amplitude; AHP₅₀, afterhyperpolarization duration to 50% recovery; HTM, high threshold mechanoreceptor neurons; LTM, low threshold mechanoreceptor neurons; UN, unresponsive neurons.

Figure 5

Comparison of dorsal root conduction velocity of dorsal root ganglion neurons between control and neuropathic rats. Scatter plots show the distribution of variables with the median (horizontal line) superimposed in each case. Details are the same as in Figure 2. Notes: Asterisks above the graph indicate the significant difference between control and neuropathic animals: *P < 0.05, **P < 0.01; ***P < 0.001. The absence of an asterisk indicates lack of a statistically significant difference.