Search

Heterotopic noxious counter-stimulation (HNCS) inhibits pain and pain processes through cerebral and cerebrospinal mechanisms. However, it is unclear whether HNCS inhibits non-nociceptive processes, which needs to be clarified for a better understanding of HNCS analgesia. The aim of this study was to examine the effects of HNCS on perception and scalp somatosensory evoked potentials (SEPs). Seventeen healthy volunteers participated in two counter-balanced sessions, including non-nociceptive (selective Aβ-fibre activation) or nociceptive electrical stimulation, combined with HNCS. HNCS was produced by a 20-min cold pressor test (left hand) adjusted individually to produce moderate pain (mean ± SEM: 42.5 ± 5.3 on a 0-100 scale, where 0 is no pain and 100 the worst pain imaginable). Non-nociceptive electrical stimulation was adjusted individually at 80% of pain threshold and produced a tactile sensation in every subject. Nociceptive electrical stimulation was adjusted individually at 120% of RIII-reflex threshold and produced moderate pain (45.3 ± 4.5). Shock sensation was significantly decreased by HNCS compared with baseline for non-nociceptive (P

The role of spinal α 2‐adrenoceptors in mediating long‐lasting modulation of hind limb withdrawal reflexes following acute noxious chemical stimulation of distant heterotopic and local homotopic locations has been investigated in pentobarbitone‐anaesthetized rabbits. Reflexes evoked in the ankle extensor muscle medial gastrocnemius (MG) by electrical stimulation of the ipsilateral heel, and reflexes elicited in the ankle flexor tibialis anterior and the knee flexor semitendinosus by stimulation at the base of the ipsilateral toes, could be inhibited for over 1 h after mustard oil (20%) was applied to either the snout or into the contralateral MG. The heel–MG response was also inhibited after applying mustard oil across the plantar metatarsophalangeal joints of the ipsilateral foot, whereas this homotopic stimulus facilitated both flexor responses. Mustard oil also caused a significant pressor effect when applied to any of the three test sites. The selective α2‐adrenoceptor antagonist, RX 821002 (100–300 μg, intrathecally), had no effect on reflexes per se, but did cause a decrease in mean arterial blood pressure. In the presence of the α2‐blocker, inhibitory and facilitatory effects of mustard oil on reflexes were completely abolished. These data imply that long‐lasting inhibition of spinal reflexes following acute noxious stimulation of distant locations involves activation of supraspinal noradrenergic pathways, the effects of which are dependent on an intact α2‐adrenoceptor system at the spinal level. These pathways and receptors also appear to be involved in facilitation (sensitization) as well as inhibition of reflexes following a noxious stimulus applied to the same limb.

The participation of the hypothalamic paraventricular nucleus (PVN) in an endogenous central mechanism of analgesia has been observed using rats in various experimental procedures including electrophysiological and behavioral tests. However, little is known about the PVN neuronal responses to noxious stimulation. The only data available indicate a c-fos increase after noxious visceral stimulations. Our electrophysiological recordings of single PVN cells showed that, out of 223 cells, 79 responded to noxious mechanical and/or thermal stimuli, and another 10 responsive cells were found in the Reuniers thalamic nucleus. These cells responded only to noxious stimuli mainly in the ipsilateral hind limb but we also observed cells responding to stimulation of both hind limbs and also the tail. Mechanical stimulation was most effective but some cells could respond to both mechanical and thermal noxious stimuli. Some of the responding PVN cells were identified by antidromic stimulation in the ipsilateral lumbar dorsal horn spinal cord. Finally, in order to document the nature of the neurotransmitter and the projection to the spinal cord of the PVN cells that responded to noxious stimulation, we used a juxtacellular approach to record and stain some neurons and found them to be oxytocinergic by immunofluorescence procedures. The PVN cells activated by noxious stimuli may suppress the peripheral incoming afferent A-delta and C fibers, completing a circuit involved in diffuse endogenous analgesia. This mechanism strongly suggests that the PVN participates in a homeostatic mechanism involved in pain and analgesia.

Various hypotheses have been proposed to account for the mechanical hyperalgesia and spontaneous pain seen in animal models of peripheral neuropathy. The purpose of the present study was to determine whether there exists a spinal neuronal correlate to these properties. An experimental neuropathy was induced in male Sprague-Dawley rats by placing a 2-mm PE-90 polyethylene cuff around the sciatic nerve. All rats were subsequently confirmed to exhibit mechanical allodynia in the von Frey test. After induction of anaesthesia with pentobarbital and acute spinalization at T9, electrophysiological experiments were performed, recording extracellular single unit activity from ipsi- and contralateral wide dynamic range dorsal horn neurons in spinal segments L1-4. On-going activity was greater in short-term (11-22 days after cuff implantation) and long-term (42-52 days) cuff-implanted rats; 38 spikes/s in short-term versus 19 spikes/s in controls; 29 spikes/s in long-term ipsi- and contralateral neurons. Receptive fields in controls were always restricted, but in almost all cuff-implanted rats extended over the whole hind paw. Responses to noxious mechanical (pinch) and noxious heat stimulation of the cutaneous receptive field in controls consisted of the typical fast initial discharge followed by an afterdischarge. In all neurons from cuff-implanted rats the initial discharge resembled that in controls. However, the afterdischarge, particularly that in response to noxious pinch, was markedly greater in both magnitude and duration. It is suggested that the greater on-going discharge is the cellular correlate of spontaneous pain, and the potentiation of the afterdischarge in response to noxious stimulation is the correlate of hyperalgesia. Given that acutely spinalized rats were tested, only peripheral and/or spinal mechanisms can be considered to explain these data. Considering all the data, it can be concluded that there is a greater change in fibres mediating noxious mechanical than noxious thermal inputs. Among different hypotheses, the one with which the present data are most compatible is that which proposes that chronic nerve injury or inflammation induces phenotypic changes predominantly in myelinated afferents. There may be a redistribution of membrane-bound ion channels, predominantly sodium channels, which leads to ectopic activity and thus spontaneous discharge of dorsal horn neurons. With regard to mechanical stimulation-evoked synaptic input, the central terminals of myelinated afferents expand into regions of the spinal cord which normally receive their predominant input from unmyelinated nociceptive afferents. This may be coupled with a change in these myelinated afferents so that they now synthesize and release peptides, primarily substance P, from their central terminals with the result that the effects of their chemical mediators of synaptic transmission add to the effects of nociceptive inputs leading to exaggerated responses to painful stimuli, thus the basis of clinical hyperalgesia.