Since its introduction in 1992, the SNL model of neuropathic pain has been widely used for various investigative works on neuropathic pain mechanisms and in screening tests for the development of new analgesic drugs [1,2,3,4].
Researchers using the SNL model have traditionally relied upon simple reflex tests such as the paw withdrawal test to assess neuropathic pain because the SNL model does not show any motor deficit [4]. However, such responses to evoked pain do not closely match the experience of continuous pain because they detect only spinal reflex and not the excitation by filament stimulation [2, 3, 8, 9, 12]. The SNL model basically has no motor deficit [3, 4]. These methods are therefore unsuitable for the clinical assessment of allodynia and chronic pain because they do not evaluate the animal’s pain behavior [5]. Gait analysis is promising for the evaluation of neurological deficits as gait is a fundamental, physiological and unforced form of locomotion with direct clinical relevance. 3D digital gait analysis could be a useful tool for detecting the severity of neuropathic pain and the change in gait characteristics following SNL [11, 14,15,16,17,18,19,20,21,22,23,24]. Indeed, some authors claim that 2D catwalk analysis is useful for assessing animal pain [9, 10, 12, 13], and these types of measures are relatively easy to assess [13, 21].
Quantitative measures available from 3D gait analysis include phase lag, symmetry, complexity and range of motion [16,17,18, 23, 24]. Left–right symmetry is perhaps the most easily identifiable measurement. Uninjured individuals tend to have gait patterns that exhibit left–right symmetry [16, 17]. Moreover, subtle changes in walking rhythm and other detailed patterns can be revealed by the Kinema-Tracer system with 3D dimensional data following injury [16, 17]. Previous papers revealed the improved toe clearance and touchdown phase of both hind-limbs following treatment in the field of spinal cord injury [15,16,17]. In addition, several papers showed the recovery of gait pattern objectively using 3D gait analysis following the treatment of neurodegenerative disorders [18, 24].
In the present study, we provided several new parameters in 3D gait analysis of an SNL model: the sagittal trajectories of each joint and the vertical instability, the heel step length, the both-foot contact time and the circular phase. First, we showed the sagittal trajectories of hind-limb joints and the characteristics of SNL hind-limb motion. The 3D dimensional data quantified the slight vertical fluctuations and the characteristic trajectories of each joint in walking. The top minus bottom height of the left hip marker was 1.47 ± 0.33 cm at 1 week post-operation and 1.30 ± 0.25 cm at 4 weeks post-operation. Compared to sham left hind-limbs, 1.47 vs. 1.0 cm and 1.30 vs. 1.0 cm, respectively, both fluctuations were significantly different. Similarly, the left knee marker values in the SNL rats were 1.80 ± 0.32 cm at 1 week post-operation and 1.88 ± 0.45 cm at 4 weeks post-operation and were significantly different, 1.80 vs. 1.20 cm and 1.88 vs. 1.28 cm. These data objectively indicate the fluctuations of the hip and knee joints during walking in SNL rats. A previous paper reported that toe and ankle angles were decreased in SNL rats in a 3D kinematic analysis [25]; however, there were no data on vertical fluctuations in each joint correlating with walking characteristics in patients with neuropathic pain.
Second, we revealed that heel step length and both-foot contact time were significantly longer on the left compared to the right side in the SNL rats. Third, in the circular phase, the R values were also decreased in the SNL rats. The ratio of the right/left circular time was 0.62 ± 0.15 in the SNL rats. These data indicate that the walking patterns of the left and right lower limbs in SNL rats are asymmetrically different from those of the sham rats. Some papers measured step length and both-foot contact time in a 2D catwalk system and obtained results similar to ours [9, 12]. However, a report by Kanchiku et al. was the first report to reveal asymmetrical walking disability by calculating the R values in the circular phase [17].
There are some limitations to the collection of accurate data with 3D kinematic gait analysis. Researchers need to train rodents to walk on the treadmill smoothly, to attach markers correctly to each joint, and to train themselves in the tracing examination processes [21]. Furthermore, the high cost of 3D kinematic analysis equipment may impede its popularization and limit its use in relevant studies. However, this new analysis system for SNL and neuropathic pain in an experimental model could contribute to the development of new treatments for patients with sciatic nerve damage and neuropathic pain because we can evaluate the rodent model using clinically relevant methods that have never been available before.