Activation Of Diffuse Noxious Inhibitory Controls Research Articles

Spinal μ and δ opioids inhibit both thermal and mechanical pain in rats.

The expression and contribution of μ (MOPR) and δ opioid receptors (DOPR) in polymodal nociceptors have been recently challenged. Indeed, MOPR and DOPR were shown to be expressed in distinct subpopulation of nociceptors where they inhibit pain induced by noxious heat and mechanical stimuli, respectively. In the present study, we used electrophysiological measurements to assess the effect of spinal MOPR and DOPR activation on heat-induced and mechanically induced diffuse noxious inhibitory controls (DNICs). We recorded from wide dynamic range neurons in the spinal trigeminal nucleus of anesthetized rats. Trains of 105 electrical shocks were delivered to the excitatory cutaneous receptive field. DNICs were triggered either by immersion of the hindpaw in 49°C water or application of 300 g of mechanical pressure. To study the involvement of peptidergic primary afferents in the activation of DNIC by noxious heat and mechanical stimulations, substance P release was measured in the spinal cord by visualizing neurokinin type 1 receptor internalization. We found that the activation of spinal MOPR and DOPR similarly attenuates the DNIC and neurokinin type 1 receptor internalization induced either by heat or mechanical stimuli. Our results therefore reveal that the activation of spinal MOPR and DOPR relieves both heat-induced and mechanically induced pain with similar potency and suggest that these receptors are expressed on polymodal, substance P-expressing neurons.

Effects of diffuse noxious inhibitory controls on temporal summation of the RIII reflex in humans

The aim of this study was to investigate the effects of diffuse noxious inhibitory controls (DNICs) on the temporal summation of the nociceptive flexion reflex (RIII reflex) in humans. Recordings were obtained from 36 healthy adults (16 M, 20 F), and the area and temporal summation threshold (TST) of the RIII reflex were measured. The subjective intensity of the painful sensation was rated on an 11-point visual analogue scale (VAS). Neurophysiological and VAS measurements were recorded after activation of DNICs by means of the cold pressor test (CPT), which involved immersing the hand in cold water (2–4 °C). A slight significant lower TST was found in the females versus the males. In all the subjects, the CPT induced a significant TST increase and RIII area reduction compared with the control session. The VAS results paralleled those of the RIII reflex area and TST. During the CPT, a significant difference in the percentage TST increase emerged between females and males, being lower in the former. Similarly, we found a significantly lower percentage reduction of the RIII area in women than in men during the CPT. To summarize, activation of DNICs through the CPT significantly increased the TST of the RIII reflex in healthy subjects. This inhibitory effect was gender-specific. Whereas other findings are based on psychophysical evaluations, the results of this experimental study provide an objective neurophysiological demonstration that DNICs attenuate temporal summation in humans and confirm the presence of significant differences in pain modulation mechanisms between men and women.

Chapter 20 Electrophysiological evidence for the activation of descending inhibitory controls by nociceptive afferent pathways

Publisher Summary This chapter presents the electrophysiological evidence for the activation of descending inhibitory controls by nociceptive afferent pathways. The three routes of administration of morphine used for alleviating pain in man—systemic, intrathecal, intracerebroventricular (ICV)—can be correlated with a reduction of diffuse noxious inhibitory controls (DNIC). The two opposite manipulations, the activation of DNIC by counter irritation procedures and its blocking by morphine, lead in therapeutic terms to the same end point—that is, hypoalgesia. This anomaly reflects the complexity of the spinal systems and provides an insight into the role of the convergent neurons in the encoding of nociceptive and non-nociceptive sensory information. The existence within a neuronal population, of gradients of activity, at least for convergent cells in the rat, should be taken into consideration in pharmacological and biochemical studies concerning nociceptive transmission toward higher centers. The future trends of the research lie in determining the supraspinal circuitry that subserves DNIC.