Three-dimensional analysis of the characteristics of joint motion and gait pattern in a rodent model following spinal nerve ligation

Abstract

Background The spinal nerve ligation (SNL) rat is well known as the most common rodent model of neuropathic pain without motor deficit. Researchers have performed analyses using only the von Frey and thermal withdrawal tests to evaluate pain intensity in the rat experimental model. However, these test are completely different from the neurological examinations performed clinically. We think that several behavioral reactions must be observed following SNL because the patients with neuropathic pain usually have impaired coordination of the motions of the right–left limbs and right–left joint motion differences. In this study, we attempted to clarify the pain behavioral reactions in SNL rat model as in patients. We used the Kinema-Tracer system for 3D kinematics gait analysis to identify new characteristic parameters of each joint movement and gait pattern. Results The effect of SNL on mechanical allodynia was a 47 ± 6.1% decrease in the withdrawal threshold during 1–8 weeks post-operation. Sagittal trajectories of the hip, knee and ankle markers in SNL rats showed a large sagittal fluctuation of each joint while walking. Top minus bottom height of the left hip and knee that represents instability during walking was significantly larger in the SNL than sham rats. Both-foot contact time, which is one of the gait characteristics, was significantly longer in the SNL versus sham rats: 1.9 ± 0.15 s vs. 1.03 ± 0.15 s at 4 weeks post-operation (p = 0.003). We also examined the circular phase time to evaluate coordination of the right and left hind-limbs. The ratio of the right/left circular time was 1.0 ± 0.08 in the sham rats and 0.62 ± 0.15 in the SNL rats at 4 weeks post-operation. Conclusions We revealed new quantitative parameters in an SNL rat model that are directly relevant to the neurological symptoms in patients with neuropathic pain, in whom the von Frey and thermal withdrawal tests are not used at all clinically. This new 3D analysis system can contribute to the analysis of pain intensity of SNL rats in detail similar to human patients’ reactions following neuropathic pain.

Reference intervals and sources of variation of pressure pain threshold for quantitative sensory testing in a Japanese population

“…The handheld algometer we used calculates PPTs on super cial tissue that equate to one point of skin tenderness as found clinically when assessing a painful area [16][17][18][19][20]. It also includes measures of temporal summation by wind-up and documentation of dynamic mechanical allodynia [18][19][20][21][22][23]. When appropriate standards are applied, PPTs can provide important and unique information about the functional status of the somatosensory system, which would complement already existing clinical methods [20][21][22].…”

“…Several studies of PPTs were reported previously in the study of LBP in western countries [5,15,[17][18][19][20][21][22][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]. All of the studies used healthy control data to compare with the data of the patients with LBP [15,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. PPT data using manual/electronic pressure algometry and cross-friction algometry in healthy control subjects from the lower back and QC or hip, gluteus maximus, or femur were reported.…”

“…The average values for all ages were as follows: PVM PPT-PVM, 539 kPa; PPT-MGM, 519 kPa; PPT-QC, 366 kPa; PPT-TA, 455 kPa; and PPT-TL, 368 kPa. We reviewed the previously published data in healthy control subjects measured by the instrument: The range of PPTs at the lumbar area was 299-628 kPa, that at the gluteal areas was 535.9-863.97 kPa, and that at the lower leg was 321.8-771.5 kPa [5,15,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. There were some differences between the articles depending on the volunteers' backgrounds.…”

Tuina for peripherally-induced neuropathic pain: A review of analgesic mechanism

“…Spinal nerve ligation (SNL) is a model for simulating spinal nerve injury, which shows typical pNP manifestations, such as spontaneous pain, thermal hyperalgesia, mechanical hyperalgesia, etc. (Seto et al, 2021). A study showed that 14 days after modeling, the mRNA expression of TLR4, IRAK1, and TRAF6 were significantly increased in SNL rats, and the expression levels of TNF-α and IL-6 also increased.…”

Glycinergic Modulation of Pain in Behavioral Animal Models

“…Spinal nerve ligation (SNL) is another model of neuropathic pain, developed by Kim and Chung (1992) , where the L5 and L6 spinal nerves are tightly ligated and also produce significant mechanical allodynia. This procedure requires high technical skill to avoid damage to the L4 nerve which can abolish allodynia and cause motor deficits ( Challa, 2015 ; Seto et al, 2021 ). This model has been used in rats to indicate glycinergic neurotransmission in the pathophysiology of pain, whereby oral or S.C. administration of the GlyT2 inhibitor opiranserin reduced mechanical allodynia in the von Frey assay ( Pang et al, 2012 ).…”