Quantitative assessment of the nociceptive withdrawal reflex in healthy, non-medicated experimental sheep

Abstract

20This study aimed to characterize the nociceptive withdrawal reflex (NWR) and to define the 21 nociceptive threshold in 25 healthy, non-medicated experimental sheep in standing posture. 22Electrical stimulation of the dorsal lateral digital nerves of the right thoracic and the pelvic limb 23 was performed and surface-electromyography (EMG) from the deltoid (all animals) and the 24 femoral biceps (18 animals) or the peroneus tertius muscles (7 animals) was recorded. The 25 behavioural reaction following each stimulation was scored on a scale from 0 (no reaction) to 5 26 (strong whole body reaction). A train-of-five 1 ms constant-current pulse was used and current 27 intensity was stepwise increased until NWR threshold intensity was reached. The NWR 28 threshold intensity (I t ) was defined as the minimal stimulus intensity able to evoke a reflex with 29 a minimal Root-Mean-Square amplitude (RMS A ) of 20 µV, a minimal duration of 10 ms and a 30 minimal reaction score of 1 (slight muscle contraction of the stimulated limb) within the time 31 window 20 to 130 ms post-stimulation. Based on this value, further stimulations were 32 performed below (0.9I t ) and above threshold (1.5I t and 2I t ). The stimulus-response curve was 33 described. Data are reported as medians and interquartile ranges. 34At the deltoid muscle I t was 4.4 mA (2.9-5.7) with an RMS A of 62 µV (30-102

Repeated electrical stimulations as a tool to evoke temporal summation of nociceptive inputs in healthy, non-medicated experimental sheep

“…The epoch of 20-130 ms post-stimulation used in this study to identify the NWR indicates that most probably the reflex originates from activation of A-delta fibres [15]. Wind-up was originally believed to result from repetitive C-fibre stimulation only [25] but when A-delta fibres were stimulated at a minimal frequency of 0.3 Hz an occurrence of wind-up occurs was demonstrated for these fibres as well [26].…”

“…In humans, the NWR threshold was found to correlate with the pain threshold [13,14]. The species-specific characteristics of the NWR after single stimulation have been evaluated in sheep in a previous study [15].…”

“…First, the nociceptive threshold (I t ) was determined as previously reported [15]. In brief, nociceptive withdrawal reflexes were evoked in sequence by electrical stimulation of the lateral digital nerves of the thoracic and the pelvic limb.…”

“…To better understand the reflex patterns, the amplitude of the EMG activity recorded in the NWR interval after the first stimulus was compared with the amplitude of the maximal NWR within the stimulation series. The post-NWR interval was evaluated to prove the correctness of the NWR interval as only the time window of 20-130 ms was expected to be originated by reflexive activation of A-delta fibres while the window of 130-200 ms could potentially be influenced by supraspinal activation [15].…”

Current and Future Issues in the development of spinal agents for the management of pain

“…Particularly with regard to pharmacokinetic profiles, large animal models such as dogs, sheep, and primates offer similar metabolic functions [458,475]. Experimental threshold models have been described for these species (see, for example, in dog [476][477][478] and in sheep [479,480]. Such models, while useful, may not capture the complexities of the inflammatory/nerve injury pain states.…”