The pathogenesis of CAI is very complicated. Most ankle sprains influenced the anterior talofibular ligament. Therefore, we tested the CPT values in this area of the injured and uninjured ankle. The results showed that compared to healthy controls, patients with CAI had higher CPT values at 250 Hz and 5 Hz electrical stimuli, which were related to fast-pain related myelinated A-delta and slow-pain related C fibers of the sensory nerve, respectively.
Sensory disorder is one of the pathophysiologic changes in CAI. Due to injury to the receptors in the ligaments, capsule, and tendons of the ankle, sensory function becomes impaired . Receptors include mechanoreceptors and nociceptors. Mechanoreceptors received tactile, pressure, and motor information. Nociceptors received thermal and pinprick information.
Using the CPT tests, the different subgroups of sensory nerve fibers could be directly stimulated and tested. The Neurometer® CPT/C can stimulate 3 types of sensory nerve fibers. Thus, the quantitative evaluation of different sensory nerves is available. Griffioen et al  showed higher CPT under 2000 Hz and 250 Hz stimuli in patients with chronic pain following lower extremity fracture. Liao et al  measured CPT in trigeminal neuralgia patients and found that CPT under 5 Hz stimulus decreased in the acute stage but increased in the chronic stage. In our study, CAI patients showed increased CPT values under 250 Hz and 5 Hz stimuli.
Previous studies have reported postural control deficits of the bilateral limb after unilateral ankle sprain and CAI, suggesting central organization altered after ankle sprain [7, 23]. Terada et al  used transcranial magnetic stimulation to evaluate corticospinal excitability and reported a potential increase in corticospinal inhibition in CAI. Rosen et al  used functional near-infrared spectroscopy to study cortical activation and found larger cortical activation variability in CAI. A systematic review reported decreased neural excitability of the soleus and the fibularis longus in CAI patients using the H-reflex, a spinal reflex . Consistently, in our study, both the injured and uninjured sides showed increased CPT values under 250 Hz and 5 Hz stimuli, and these changes suggested central sensory adaption in CAI.
In consideration of gender, age and BMI effects, previous studies showed inconsistent results. Uddin et al  reported that age and gender were not correlated with CPT scores. Nakatani-Enomoto et al  reported higher CPT in men than in women and in older individuals than in young subjects. In this study, there was no correlation between gender, age and BMI factors and CPT values at any frequency. The inconsistency may be due to the different sample sizes and objectives of the studies.
Correlations among CPT values at different frequencies were found in our study. Participants with higher CPT values under one frequency showed trends of higher CPT values under other frequencies. This may be caused by individual variability. The correlations may reflect the consistency of the sensory threshold test using CPT measurements.
However, there are some disadvantages in CPT tests. These testing procedures require participant reaction and feedback, similar to the hearing test. Thus, they are not entirely objective methods. Nerve conduction velocity measured by electromyography is an objective measurement, but until now, there have been reports of lower motor nerve conduction velocity  rather than sensory nerve studies. The conduction velocity can reflect the function of large myelinated fibers .
There are some limitations in this study. First, this was a case-control study conducted in a tertiary referral center, and unknown selection bias might have affected the study results. Second, only CPT values at the anterior talofibular ligament region were measured, and future studies are needed to investigate the CPT values at more sites of the lower extremities in CAI subjects. Studies of the relations between CPT and other sensory tests are also needed.