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

Figures & data

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.

Table 1 Comparison of properties of high-threshold mechanoreceptive and low-threshold mechanoreceptive dorsal root ganglion neurons between control and neuropathic rats

CV range	Receptor class	Model	n	CV (m/s)	Vm (–mV)	APA (mV)	APdB (ms)	APRT (ms)	APFT (ms)	MRR (mV/ms)	MFR (mV/ms)	AHPA (mV)	AHP50 (ms)
C	HTM	Control	21	0.59 ± 0.040	62.12 ± 2.130	83.80 ± 2.092	3.76 ± 0.247	l.47 ± 0.092	2.27 ± 0.181	146.5 ± 8.587	60.89 ± 3.390	8.73 ± 0.877	11.14 ± 1.888
		NeP	28	0.60 ± 0.036	60.35 ± 1.626	77.58 ± 2.725	3.99 ± 0.296	1.41 ± 0.111	2.40 ± 0.210	151.5 ± 10.81	58.04 ± 3.039	9.68 ± 0.771	10.95 ± 1.614
				P = 0.8355	P = 0.5061	P = 0.0934	P = 0.5741	P = 0.6801	P = 0.6515	P = 0.7354	P = 0.5356	P = 0.4217	P = 0.9417
	LTM	Control	8	0.47 ± 0.058	72.79 ± 1.866	70.89 ± 3.526	3.37 ± 0.273	1.28 ± 0.096	2.16 ± 0.177	161.5 ± 18.85	73.94 ± 1.437	1.40 ± 0.437	10.05 ± 1.054
		NeP	8	0.50 ± 0.033	71.62 ± 1.817	71.10 ± 2.91	3.19 ± 0.267	1.30 ± 0.052	2.26 ± 0.236	173.4 ± 10.91	71.27 ± 1.84	1.78 ± 0.347	9.68 ± 0.861
				P = 0.6855	P = 0.6583	P = 0.9579	P = 0.6361	P = 0.8836	P = 0.7336	P = 0.5925	P = 0.2878	P = 0.5069	P = 0.7869
	Unresponsive	Control	4	0.60 ± 0.054	59.67 ± 5.840	82.71 ± 4.650	3.74 ± 0.429	1.45 ± 0.246	2.18 ± 0.826	147.7 ± 22.08	68.29 ± 5.938	8.67 ± 3.346	11.56 ± 2278
		Nep	4	0.61 ± 0.094	59.59 ± 6.306	74.37 ± 7.491	3.95 ± 1.139	l.44 ± 0.334	2.10 ± 0.686	154.0 ± 43.60	59.51 ± 4.406	8.09 ± 1.659	11.86 ± 2.856
				P = 0.9469	P = 0.9933	P = 0.3811	P = 0.8718	P = 0.9769	P = 0.9377	P = 0.9016	P = 0.2801	P = 0.8802	P = 0.9372
Aσ	HTM	Control	11	4.32 ± 0.514	53.96 ± 3.875	74.70 ± 3.300	2.49 ± 0.289	1.03 ± 0.123	1.40 ± 0.204	193.5 ± 13.69	84.53 ± 12.50	9.51 ± 1.494	9.68 ± 2.241
		NeP	7	4.86 ± 0.505	53.86 ± 3.341	78.75 ± 3.829	3.87 ± 0.604	1.06 ± 0.075	2.66 ± 0.518	168.3 ± 23.21	62.09 ± 9.594	9.68 ± 2.564	8.32 ± 1.910
				P = 0.4871	P = 0.9867	P = 0.4429	P = 0.0355*	P = 0.8692	P = 0.0180*	P = 0.3311	P = 0.2189	P = 0.9519	P = 0.6776
	LTM	Control	7	5.17 ± 0.705	70.65 ± 4.122	66.92 ± 3.867	1.76 ± 0.155	0.77 ± 0.081	0.98 ± 0.098	202.8 ± 15.22	123.1 ± 7.946	5.72 ± 1.695	3.22 ± 0.628
		NeP	9	3.91 ± 0.500	62.23 ± 2.126	62.59 ± 2.602	2.51 ± 0.412	0.93 ± 0.092	1.58 ± 0.387	148.0 ± 13.37	89.84 ± 8.396	7.44 ± 1.463	4.14 ± 1.255
				P = 0.1548	P = 0.0727	P = 0.3519	P = 0.1472	P = 0.2291	P = 0.2091	P = 0.170*	P = 0.0138*	P = 0.4545	P = 0.5601
	Unresponsive	Control	3	3.21 ± 1.084	54.16 ± 4.564	75.26 ± 5.250	1.98 ± 0.262	0.88 ± 0.15	1.14 ± 0.205	195.5 ± 17.24	76.23 ± 21.145	8.54 ± 3.340	12.87 ± 3.639
		NeP	3	4.14 ± 1.472	53.28 ± 3.183	79.11 ± 5.968	2.71 ± 0.619	1.17 ± 0.06	2.77 ± 0.758	163.1 ± 26.37	74.371 ± 10.165	10.34 ± 3.344	13.3 ± 2.652
				P = 0.6365	P = 0.8704	P = 0.6449	P = 0.1616	P = 0.2445	P = 0.0834	P = 0.3204	P = 0.6313	P = 0.7617	P = 0.9266
Aβ	HTM	Control	26	12.42 ± 0.548	62.80 ± 2.280	75.18 ± 2.116	1.73 ± 0.061	0.71 ± 0.041	1.02 ± 0.032	262.9 ± 14.87	141.9 ± 9.230	9.39 ± 0.614	10.69 ± 1.551
		NeP	39	11.38 ± 0.504	63.21 ± 1.783	75.47 ± 1.674	2.45 ± 0.146	0.86 ± 0.054	1.58 ± 0.132	211.5 ± 11.07	94.47 ± 9.214	6.57 ± 0.765	8.98 ± 0.931
				P = 0.1794	P = 0.8863	P = 0.9127	P = 0.0003***	P = 0.0492*	P = 0.0012**	P = 0.0281*	P = 0.0118*	P = 0.0101*	P = 0.3184
	LTM (SKIN)	Control	50	17.02 ± 0.469	68.63 ± 1.100	63.09 ± 1.508	1.25 ± 0.038	0.49 ± 0.019	0.76 ± 0.028	262.4 ± 8.735	142.7 ± 4.855	5.51 ± 0.493	5.42 ± 0.834
		NeP	63	14.70 ± 0.548	65.63 ± 0.962	63.16 ± 1.292	1.48 ± 0.065	0.57 ± 0 019	0.90 ± 0.050	226.2 ± 7.947	131.7 ± 5.882	4.89 ± 0.365	5.65 ± 0.743
				P = 0.0023**	P = 0.0423*	P = 0.9704	P = 0.0046*	P = 0.0027**	P = 0.0222*	P = 0.0027**	P = 0.1641	P = 0.3045	P = 0.8398
	LT (MS)	Control	36	18.76 ± 0.638	66.47 ± 1.704	57.83 ± 0.929	0.96 ± 0.032	0.43 ± 0.017	0.53 ± 0.022	258.4 ± 12.44	186.0 ± 8.476	6.73 ± 0.678	1.58 ± 0.114
		NeP	53	16.69 ± 0.599	62.60 ± 1.055	56.63 ± 1.107	1.10 ± 0.045	0.49 ± 0.016	0.62 ± 0.033	225.9 ± 8.019	155.0 ± 5.126	7.07 ± 0.581	2.20 ± 0.146
				P = 0.0235*	P = 0.0442*	P = 0.4422	P = 0.0229*	P = 0.0152*	P = 0.0467*	P = 0.0239*	P = 0.0013**	P = 0.7089	P = 0.0030**
	Unresponsive	Control	8	12.67 ± 0.831	63.48 ± 2.774	81.95 ± 2.107	1.63 ± 0.062	0.63 ± 0.021	1.03 ± 0.048	258.4 ± 13.18	133.5 ± 7.025	8.34 ± 0.719	10.26 ± 3.545
		NeP	9	11.15 ± 1.088	61.03 ± 3.482	79.13 ± 3.438	2.29 ± 0.251	0.77 ± 0.093	1.53 ± 0.260	221.4 ± 23.38	104.8 ± 15.18	5.23 ± 1.207	9.74 ± 1.805
				P = 0.2922	P = 0.5966	P = 0.5083	P = 0.0297*	P = 0.1891	P = 0.0948	P = 0.2023	P = 0.1270	P = 0.0487*	P = 0.8933

Notes: Statistical tests for each variable were made in all subgroups comparing neurons in control and neuropathic rats. The means ± standard deviations of variables measured are given. The value of P (mean-Whitney) is shown below each section. The asterisks show the level of significance of the difference between neurons in control and neuropathic animals:

* P < 0.05;

** P < 0.01;

*** P < 0.001.

Abbreviations: n, the number of neurons in each group; CV, conduction velocity; Vm, resting membrane potential; APA, action potential amplitude; APdB, action potential duration at base; APRT, action potential rise time; APFT, action potential fall time; MRR, maximum rising rate; MFR, maximum falling rate; AHPA, afterhyperpolarization amplitude; AHP₅₀, afterhyperpolarization duration at 50% recovery; HTM, high threshold mechanoreceptive neurons; LTM, low threshold mechanoreceptive neurons; UN, unresponsive neurons; MS, muscle spindle 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.

Table 2 Locations of receptive fields of high-threshold mechanoreceptors and low-threshold mechanoreceptors in controls and neuropathic rats

CV range	Receptor class	Model	n	Foot	Calf	Thigh	Ankle joint	Knee joint
C	HTM	Control	21	8	5	4	2	2
		NeP	28	12	4	6	4	2
	LTM	Control	8	5	2	1	/	/
		NeP	8	6	/	2	/	/
Aσ	HTM	Control	11	5	3	3	/	1
		NeP	7	4	2	1	/	/
	LTM	Control	7	2	3	2	/	/
		NeP	9	2	4	3	/	/
Aβ	HTM	Control	26	4	6	8	4	4
		NeP	39	3	9	12	3	2
	LTM (GF)	Control	20	4	6	8	1	1
		NeP	25	3	5	13	2	1
	LTM (RA)	Control	20	10	1	2	1	2
		NeP	24	9	1	3	2	1
	LTM (SA)	Control	10	9	/	/	1	/
		NeP	14	12	/	/	2	/
	LTM (MS)	Control	36	2	25	9	/	/
		NeP	53	3	40	10	/	/

Abbreviations: HTM, high threshold mechanoreceptive neurons; LTM, low threshold mechanoreceptive neurons; MS, muscle spindle neurons; RA, rapidly adapting neurons; SA, slowly adapting neurons; GF, guard/field neurons.