Activation of the descending pain modulatory system using cuff pressure algometry: Back translation from man to rat

Abstract

Background

Diffuse noxious inhibitory controls (DNIC) as measured in rat and conditioned pain modulation (CPM), the supposed psychophysical paradigm of DNIC measured in humans, are unique manifestations of an endogenous descending modulatory pathway that is activated by application of a noxious conditioning stimulus. The predictive value of the human CPM processing is crucial when deliberating the translational worth of the two phenomena.

Methods

For CPM or DNIC measurement, test and conditioning stimuli were delivered using a computer‐controlled cuff algometry system or manual inflation of neonate blood pressure cuffs respectively. In humans (n=20), cuff pain intensity (for pain detection and pain tolerance thresholds) was measured using an electronic visual analogue scale. In isoflurane‐anaesthetised naïve rats, nociception was measured by recording deep dorsal horn wide dynamic range (WDR) neuronal firing rates (n=7) using in vivo electrophysiology.

Results

A painful cuff‐pressure conditioning stimulus on the leg increased pain detection and pain tolerance thresholds recorded by cuff stimulation on the contralateral leg in humans by 32±3% and 24±2% (mean±SEM) of baseline responses respectively (P<0.001). This finding was back‐translated by revealing that a comparable cuff‐pressure conditioning stimulus (40 kPa) on the hind paw inhibited the responses of WDR neurons to noxious contralateral cuff test stimulation to 42±9% of the baseline neuronal response (P=0.003).

Conclusions

These data substantiate that the noxious cuff pressure paradigm activates the descending pain modulatory system in rodent (DNIC) and man (CPM), respectively. Future back and forward translational studies using cuff pressure algometry may reveal novel mechanisms in varied chronic pain states.

from Wiley: European Journal of Pain: Table of Contents https://ift.tt/2ySgtSb
via IFTTT