Evaluation of trigeminal nociceptive processing in horses

Abstract

As a result of a general increased knowledge and sensibility toward pain in humans, successful pain management in equine patients became recently an important issue. Pain recognition and assessment are the first steps to provide adequate analgesic therapy. As mechanism-based treatment options facilitate successful pain management, the investigation of the pathophysiology of neuropathic pain disorders is essential. This latter necessitate substantial understanding of physiologic function of peripheral and central nervous system. While nociceptive neurophysiology of the equine locomotor apparatus is well established, information about nociceptive processing of the trigeminal system in horses has been lacking. Electrically induced reflexes can be used to investigate the physiology and pathophysiology of the trigeminal system in humans. Similarly, the assessment of the trigemino-cervical (TCR) and blink reflexes (BR) may represent a new diagnostic tool in horses. Therefore, the first aim of our investigations was to evoke nociceptive trigeminal reflexes and describe their electrophysiological characteristics in non-sedated horses. The infraorbital (ION) and supraorbital nerves (SON) were stimulated transcutaneously in 10 adult Warmblood horses in separate sessions using train-of-five electrical pulses. The current was increased gradually until the TCR threshold was found. The stimulus–response curve of the TCR was evaluated. At the same time as TCR, the BR response was also assessed. Surface electromyographic (EMG) responses were recorded from the orbicularis oculi (OO), splenius (SPL) and cleidomastoideus (CM) muscles. Latency, duration, amplitude of the reflexes and behavioural responses were analysed. We found that noxious electrical stimulation of the ION or SON evoked reflex EMG responses, with similar features regardless of the nerve that had been stimulated. Stimulations of increasing intensity elicited reflexes of increasing amplitude and decreasing latency, accompanied by stronger behavioural reactions, therefore confirming the nociceptive nature of the TCR. Our second aim was to evaluate the effect of repeated stimulation on this nociceptive withdrawal reflex, the TCR. It is known that repeated sub-threshold nociceptive electrical stimulation results in temporal summation of the limb nociceptive withdrawal reflex and it is a well-established non-invasive model to investigate the wind-up phenomenon in horses. Due to structural similarities of the trigeminal sensory nucleus to the dorsal horn of the spinal cord, temporal summation should be evoked by repeated transcutaneous electrical stimulation of trigeminal afferents. To evaluate this hypothesis repeated transcutaneous electrical stimulation was applied to the SON and ION of 10 horses. Stimulation intensities varied between 0.5 and 1.3 times the TCR threshold defined for single stimulation (TSS). Evoked EMG activity of the OO, SPL and CM muscles was recorded and the signals analysed in the previously established epochs typical to the early and late component of the BR and to the TCR. Behavioural reactions were evaluated with the aid of numerical rating scale. We found that the nociceptive late component of the BR and the TCR were not elicited by sub-threshold intensity repeated transcutaneous electrical stimulation. Furthermore, the median reflex amplitude for the 10 horses showed a tendency to decline over the stimulation train so temporal summation of afferent trigeminal inputs could not be observed. Therefore, the modulation of trigeminal nociceptive processing attributable to repeated Aδ fibre stimulations seems to differ from spinal processing of similar inputs as it seems to have an inhibitory rather than facilitatory effect. Further evaluation is necessary to highlight the underlying mechanism. In horses affected by trigeminal pathology, altered nociceptive modulation and DNIC deficiencies could modify the neurophysiological profile observed in the healthy subjects. Therefore, our results regarding to the trigeminal nociceptive reflexes are representing a novel non-invasive tool for a mechanism-based approach to diagnosis.