Neural coding of nociceptive stimuli—from rat spinal neurones to human perception

Abstract

Translational studies are key to furthering our understanding of nociceptive signalling and bridging the gaps between molecules and pathways to the patients. This requires use of appropriate preclinical models that accurately depict outcome measures used in humans. Whereas behavioural animal studies classically involve reports related to nociceptive thresholds of, for example, withdrawal, electrophysiological recordings of spinal neurones that receive convergent input from primary afferents permits investigation of suprathreshold events and exploration of the full-range coding of different stimuli. We explored the central processing of nociceptive inputs in a novel parallel investigation between rats and humans. Using radiant laser pulses, we first compared the electrophysiological responses of deep wide dynamic range and superficial nociceptive-specific neurones in the rat dorsal horn with human psychophysics and cortical responses. Secondly, we explored the effects of spatial summation using laser pulses of identical energy and different size. We observed 3 main findings. Firstly, both rodent and human data confirmed that neodymium-yttrium aluminium perovskite laser stimulation is a nociceptive-selective stimulus that never activates Aβ afferents. Secondly, graded laser stimulation elicited similarly graded electrophysiological and behavioural responses in both species. Thirdly, there was a significant degree of spatial summation of laser nociceptive input. The remarkable similarity in rodent and human coding indicates that responses of rat dorsal horn neurones can translate to human nociceptive processing. These findings suggest that recordings of spinal neuronal activity elicited by laser stimuli could be a valuable predictive measure of human pain perception.

Diffuse noxious inhibitory controls and nerve injury

“…36 The translation of DNIC acting on deep dorsal horn neurons to humans is supported by the fact that these spinal neurons code the intensity and spatial features of stimuli under the same anaesthetic conditions, in a manner remarkably parallel to human psychophysics. 28 Indeed, a recent study in patients with diabetic neuropathy showed that tapentadol restores CPM, exactly as we found here. 24 Descending controls appear to lack strict somatotopy.…”

Spinal neuronal correlates of tapentadol analgesia in cancer pain: A back‐translational approach

“…Importantly, the recording of sensory spinal neurones under general anaesthesia allows suprathreshold stimuli, hence stimulation above the normal behavioural threshold, and so achieving levels of pain transmission that equate to the high pain scores that patients report. In fact, we have recently reported on the strong correlations between human pain ratings and the graded firing of these neurones under identical conditions (Sikandar et al, 2013). Very close parallels between both human pain perception and the human cortical response (electroencephalography measures) and spinal wide dynamic range (WDR) neuronal coding in rats were observed.…”

Novel TRPM8 Antagonist Attenuates Cold Hypersensitivity after Peripheral Nerve Injury in Rats

“…Although TRPM8-positive afferents terminate superficially in the dorsal horn (Takashima et al, 2007), deep dorsal horn WDR neurons receive these inputs from all fiber types either directly or indirectly through interneurons. We examined nociceptive processing in secondorder neurons in the deep dorsal horn, which respond to a wide range of stimuli in an intensity-dependent manner, a feature that correlates with nociceptive processing in humans (Sikandar et al, 2013). In naive rats, neither 30 nor 100 mg/kg M8-An significantly reduced lamina V/VI WDR neuronal responses to innocuous or noxious cold stimulation.…”