Why are sensory axons more vulnerable for ischemia than motor axons?

Abstract

Objective: In common peripheral neuropathies, sensory symptoms usually prevail over motor symptoms. This predominance of sensory symptoms may result from higher sensitivity of sensory axons to ischemia.

Methods: We measured median nerve compound sensory action potentials (CSAPs), compound muscle action potentials (CMAPs), and excitability indices in five healthy subjects during forearm ischemia lasting up to disappearance of both CSAPs and CMAPs.

Results: ISCHEMIA INDUCED: (1) earlier disappearance of CSAPs than CMAPs (mean ± standard deviation 30±5 vs. 46±6 minutes), (2) initial changes compatible with axonal depolarization on excitability testing (decrease in threshold, increase in strength duration time constant (SDTC) and refractory period, and decrease in absolute superexcitability) which were all more prominent in sensory than in motor axons, and (3) a subsequent decrease of SDTC reflecting a decrease in persistent Na(+) conductance during continuing depolarisation.

Interpretation: Our study shows that peripheral sensory axons are more vulnerable for ischemia than motor axons, with faster inexcitability during ischemia. Excitability studies during ischemia showed that this was associated with faster depolarization and faster persistent Na(+) channel inactivation in sensory than in motor axons. These findings might be attributed to differences in ion channel composition between sensory and motor axons and may contribute to the predominance of sensory over motor symptoms in common peripheral neuropathies.

Figure 1. Evolution of compound motor action potential (CMAP) and compound sensory action potential (CSAP) during and after ischemia in one subject.

The CMAP disappeared after 44 minutes. The CSAP disappeared after 28 minutes. Reperfusion was started immediately after disappearance of the CMAP, with prompt reversal of CMAP and CSAP.

Figure 2. CMAP and CSAP amplitudes of median nerve axons after stimulation at the wrist in five healthy subjects.

Ischemia was induced after three minutes and lasted until disappearance of the CMAP in all subjects. Inexcitability occurred earlier in sensory than in motor nerves, reflected as disappearance of the CMAP after 46±6 minutes and the CSAP after 30±5 (mean difference 15 minutes, 95% CI 7–24). CMAP and CSAP were measured every minute and different symbols indicate different subjects: Subject (S) 1  =  female, 33 years; S2  =  female, 40 years; S3 = male, 43 years; S4  =  male, 49 years; S5 =  male 61 years.

Figure 3. Recovery cycle of motor and sensory median nerve axons stimulated at the wrist before, during, and after ischemia in one subject.

Threshold increase is plotted upwards. Before  =  before induction of ischemia; Isch1  =  from 5 to 10 minutes after the induction of ischemia; Isch2 = 15–20 minutes; Isch3 = 25–30 minutes; Isch4 = 35–40 minutes; Isch5 = 45–50 minutes; after = 5–10 minutes after release of ischemia; A = 0% refractory period; Time at first x-axis intercept  =  refractory period; B  =  superexcitability; C  =  subexcitability.

Figure 4. Strength duration time constant (SDTC), 50% refractory period, and temperature for motor and sensory axons before, during and after ischemia in four healthy subjects.

Before  =  before induction of ischemia; Isch1  =  from 5 to 10 minutes after the induction of ischemia; Isch2 = 15–20 minutes; Isch3 = 25–30 minutes; Isch4 = 35–40 minutes; Isch5 = 45–50 minutes; after = 5–10 minutes after release of ischemia. Subject (S) 2 = female, 40 years; S3 = male, 43 years; S4 = male, 49 years; S5 = male 61 years.