Nociceptive Electrical Stimulation Research Articles

Can Preoperative Electrical Nociceptive Stimulation Predict Acute Pain After Groin Herniotomy?

Preoperative identification of patients at risk for high-intensity postoperative pain may be used to predict patients at risk for development of a persistent pain state and allocate patients to more intensive specific pain therapy. Preoperative pain threshold to electrocutaneus stimulation has recently been shown to correlate to acute postoperative pain after cesarean section, but the findings have not been confirmed in larger studies or other procedures. Preoperative electrical pain detection threshold and pain tolerance were assessed in patients undergoing a primary unilateral groin hernia repair. The correlation between the pain data for electrical stimulation was compared with the postoperative pain during the first week in 165 patients, whereof 3 were excluded. Preoperative electrical pain detection threshold and electrical pain tolerance threshold did not correlate to postoperative pain (rho = -0.13, P = .09, and rho = -1.2, P = .4, respectively. Although preoperative electrical nociceptive stimulation may predict patients at risk of high-intensity acute pain after other surgical procedures, this was not the case in groin hernia repair patients receiving concomitant treatment with acetaminophen and ibuprofen.

Effects of epidural administration of dexmedetomidine on the minimum alveolar concentration of isoflurane in dogs

Objective-To evaluate the effects of epidural administration of 3 doses of dexmedetomidine on isoflurane minimum alveolar concentration (MAC) and characterize changes in bispectral index (BIS) induced by nociceptive stimulation used for MAC determination in dogs. Animals-6 adult dogs. Procedures-Isoflurane-anesthetized dogs received physiologic saline (0.9% NaCl) solution (control treatment) or dexmedetomidine (1.5 [DEX1.5], 3.0 [DEX3], or 6.0 [DEX6] mug/kg) epidurally in a crossover study. Isoflurane MAC (determined by use of electrical nociceptive stimulation of the hind limb) was targeted to be accomplished at 2 and 4.5 hours. Changes in BIS attributable to nociceptive stimulation and cardiopulmonary data were recorded at each MAC determination. Results-With the control treatment, mean +/- SD MAC values did not change over time (1.57 +/- 0.23% and 1.55 +/- 0.25% at 2 and 4.5 hours, respectively). Compared with the control treatment, MAC was significantly lower at 2 hours (13% reduction) but not at 4.5 hours (7% reduction) in DEX1.5-treated dogs and significantly lower at 2 hours (29% reduction) and 4.5 hours (13% reduction) in DEX3-treated dogs. The DEX6 treatment yielded the greatest MAC reduction (31% and 22% at 2 and 4.5 hours, respectively). During all treatments, noxious stimulation increased BIS; but changes in BIS were correlated with increases in electromyographic activity. Conclusions and Clinical Relevance-In dogs, epidural administration of dexmedetomidine resulted in dose-dependent decreases in isoflurane MAC and that effect decreased over time. Changes in BIS during MAC determinations may not represent increased awareness because of the possible interference of electromyographic activity.

Unloading reactions in functional ankle instability

Past studies have suggested that unloading reactions may be a strategy to prevent ankle sprains. This study tested unloading reactions in individuals with functional ankle instability (FAI) in order to better understand this phenomenon. We provoked unloading reactions in 20 individuals with FAI and 18 healthy controls by delivering nociceptive electrical stimulation to the lateral aspect of the ankle during standing. Ground reaction forces, lower extremity kinematics, and EMG activity of five muscles of the lower limb were recorded. Individuals with FAI demonstrated increased and faster body weight unloading after stimulation. This hyper-reactivity may partially account for the sensation of the ankle “giving way” in those with a history of severe ankle sprain and subsequent functional instability.

Small animal, whole brain fMRI: Innocuous and nociceptive forepaw stimulation

Supra-spinal pain processing involves a number of extensive networks. An examination of these networks using small animal functional magnetic resonance imaging (fMRI) is difficult. While prior studies have successfully delineated regions consistent with known pain processing pathways, they have been restricted to acquisitions of limited spatial extent with coarse in-plane resolution to achieve a high temporal resolution. An isotropic, whole brain fMRI protocol has been developed for the examination of the supra-spinal consequences of innocuous and nociceptive electrical stimulation of the rat forepaw. Innocuous electrical stimulation of the rat forepaw delineated BOLD contrast responses consistent with known somatosensory processing pathways (contralateral primary somatosensory cortex (S1), a region consistent with secondary somatosensory cortex, the ventral posterolateral thalamic nucleus and ipsilateral cuneate nucleus), providing face validity for the technique. The putative noxious stimulus delineated additional regions consistent with the classical lateral and medial pain systems as well as secondarily associated areas: the aversion and descending inhibition systems. These included the ipsilateral inferior colliculus, anterior pretectal nucleus, mediodorsal thalamic nucleus, with regions in the pre-frontal, cingulated, ventral orbital and infra-limbic cortices, nucleus accumbens all exhibiting negative BOLD changes. Such regions are in agreement with, and extend, those previously reported. Acquisition, post-processing and analysis methodologies undertaken in this study constitute a marked extension of previous fMRI in the rat, enabling whole brain coverage at a spatial resolution sufficient to delineate regional changes in BOLD contrast consistent with somatosensory and nociceptive networks.

Specific features of learning with nociceptive electrical reinforcement in rats of different genetic strains: Role of brain neurotransmitter systems

The interaction between neurotransmitter systems and opioid system in rats of different strains was studied during learning and emotional stress. The interaction between noradrenergic, serotoninergic, and opioid systems in the brain is the main neurochemical mechanism underlying learning reinforced by nociceptive electrical stimulation, which determine individual differences in the rate and type of learning.

Activation of a residual cortical network during painful stimulation in long-term postanoxic vegetative state: a 15O–H2O PET study

Survivors of prolonged cerebral anoxia often remain in the persistent vegetative state (PVS). In this study, long-term PVS patients were investigated by 15O–H2O PET to analyze their central processing of pain. The study was approved by the local Ethics Committee, the experiments were performed in accordance with the Helsinki Declaration of 2000. Seven patients remaining in PVS of anoxic origin for a mean of 1.6 years (range 0.25–4 years) were investigated. We performed functional PET of the brain using 15O-labelled water during electrical nociceptive stimulation. Additionally, a brain metabolism study using 18F–fluorodeoxyglucose (FDG) PET and multi-sequence MRI (including a 3-D data set) were acquired in all patients. PET data were analyzed by means of Statistical Parametric Mapping (SPM99) and coregistered to a study-specific brain template. MRI and FDG PET showed severe cortical impairment at the structural and the functional level, that is, general atrophy of various degrees and a widespread significant hypometabolism, respectively. Pain-induced activation (hyperperfusion) was found in the posterior insula/secondary somatosensory cortex (SII), postcentral gyrus/primary somatosensory cortex (SI), and the cingulate cortex contralateral to the stimulus and in the posterior insula ipsilateral to the stimulus (P<0.05, small-volume-corrected). No additional areas of the complex pain-processing matrix were significantly activated. In conclusion, the regional activity found at the cortical level indicates that a residual pain-related cerebral network remains active in long-term PVS patients.

End-Tidal Sevoflurane Required To Suppress Responses to Nociceptive Electrical Stimulation during Epidural Anesthesia with 0.5% and 1% Lidocaine

End-Tidal Sevoflurane Required To Suppress Responses to Nociceptive Electrical Stimulation during Epidural Anesthesia with 0.5% and 1% Lidocaine

Changes in somatosensory evoked potentials and reflectory reactions of human hand muscles to nociceptive stimulation of index finger before and during ischemia

Somatosensory evoked potentials and reflectory reaction ofm. thenar to nociceptive electrical stimulation of the index finger before and during its ischemia were studied in healthy volunteers. The amplitude of early components of the somatosensory evoked potentials N23-P31 and N50-P120 correlated with stimulus intensity, while the amplitude of N140-P200 did not depend on both stimulus intensity and pain. The nociceptive RIII reflex recorded fromm. thenar was the most reliable index of pain caused by electrical stimulation of the finger.

Repressive/defensive coping, endogenous opioids and health: how a life so perfect can make you sick

Hyperactivity of endogenous opioid systems has been postulated to mediate the associations between defensive/repressive coping styles, enhanced stress responsivity, and reduced immunocompetence. Study 1 examined whether repressive/defensive coping would be associated with greater sensitivity to opioid antagonism. Judgments of the painfulness of ascending series of electrocutaneous stimulation applied to the forearm were determined before and after the administration of naloxone and placebo in 38 men and 42 women. All subjects were healthy with a mean age of 32.9 years. Naloxone (10 mg i.v.) and placebo were administered in double-blind fashion and counterbalanced. Subjects were classified as High- and Low-defensive and repressive copers on the basis of scores on the Marlowe—Crowne Social Desirability Scale and the Balanced Inventory of Desirable Responding, respectively. High Self-Deception was associated with naloxone-induced hyperalgesia, whereas no effects of naloxone on pain ratings were observed in low-Self-Deceptive subjects. In Study 2, resting plasma β-endorphin levels were found to be positively correlated with defensiveness in men ( n = 26), but not women ( n = 44). Study 3 examined 82 healthy subjects (mean age = 28.7 years). β-Endorphin/defensiveness correlations were found to be greater following, compared to prior to, electrical nociceptive stimulation in men ( n = 49), but unrelated in women ( n = 33). These findings are consistent with the hypothesized endorphinergic dysregulation associated with repressive/defensive coping styles and are discussed in terms of the immuno-regulatory implications of such a dysregulation.

Evidence for central summation of C and Aδ nociceptive activity in man

Using two different stimulators, we have induced activity in Aδ and C afferents in order to investigate a possible summation of nociceptive activity from these two fiber types. We used nociceptive electrical stimulation to evoke activity in Aδ fibers. High-intensity light from a xenon lamp, focused into a liquid light guide which was positioned on a spot painted black under the sole of the foot, resulted in a characteristic delayed burning sensation, indicating selective C-fiber activation. By varying the delay between radiant heat and electrical stimuli (0–3000 msec), sensations evoked by these stimuli were brought to coincide. When we elicited the electrical stimulation during on-going burning pain, corresponding to a delay of approximately 1 sec between the stimulations, we found a significantly higher nociceptive withdrawal reflex in tibialis anterior ( P < 0.01) and a higher overall pain rating ( P < 0.05). The existence of a summation mechanism at the spinal cord is the most likely explanation for our findings. Furthermore, the results demonstrate that the nociceptive reflex may be modulated by on-going C-fiber activity.

EEG complexity changes related to memory processes in the hippocampal area of rats

The aim of the present study was to compare the effects of explicit suggestions of analgesia and of the activation of the Diffuse Noxious Inhibitory Control (DNIC) by cold pressor test on pain perception and heart rate in healthy participants with high (highs, N = 18), low (lows, N = 18) and intermediate scores of hypnotizability (mediums, N = 15) out of hypnosis. Pain reports and the stimulus-locked heart rate changes induced by electrical nociceptive stimulation of the left hand were studied in the absence of concomitant stimuli (Control), during suggestions of analgesia (SUGG, glove analgesia) and during cold pressor test used as a conditioning stimulus to the right hand (DNIC, water temperature = 10–12 °C) in the REAL session. Participants were submitted also to a SHAM session in which the DNIC water temperature was 30 °C and the suggestions for analgesia were substituted with weather forecast information. Both suggestions and DNIC reduced pain significantly in all subjects; however, the percentage of reduction was significantly larger in highs (pain intensity = 55% of the control condition) than in mediums (70%) and lows (80%) independently of the REAL/SHAM session and of the specific pain manipulation. Heart rate was not modulated consistently with pain experience. Findings indicate that both suggestions and DNIC influence pain experience as a function of hypnotizability and suggest that both sensory and cognitive mechanisms co-operate in DNIC induced analgesia

Diffuse noxious inhibitory controls in humans: A neurophysiological investigation of a patient with a form of Brown‐Séquard syndrome

In normal subjects, the application of heterotopic painful stimuli induces simultaneous and parallel decrease in the sensation of pain and of the spinal nociceptive flexion (RIII) reflex evoked by electrical stimulation of the sural nerve. This inhibition of the RIII reflex is absent in tetraplegic patient with clinically complete spinal cord transections and can be triggered only from the analgesic hand in patients with Wallenberg's syndrome. These findings suggest that the inhibitory phenomena observed in normal subjects are likely to be examples of diffuse noxious inhibitory controls (DNICs), being sustained by a loop involving supraspinal structures, the ascending part of which is localized in the spinoreticular tract. We now report an exceptional case of a patient with Brown-Séquard syndrome due to a 4-year-old spinal cord lesion (left side, T-6 level) produced by a knife-wound in the back. Nociceptive flexion (RIII) reflexes elicited by stimulation of cutaneous afferents in the ulnar and sural nerves were studied in the upper and lower limbs by recording from the biceps brachialis and biceps femoris muscles, respectively. For each limb, the RIII reflex threshold was determined. The reflex was then elicited regularly by stimuli of 1.2 times threshold before, during, and after periods of nociceptive electrical conditioning stimulation (15 mA; 4 Hz; 1 min) applied successively to the other three limbs.(ABSTRACT TRUNCATED AT 250 WORDS)

Augmentation of muscle nociceptive respiratory reflex facilitation by vagal afferents.

Vagal influence on the facilitation of phrenic neural activity during respiratory phase-locked, gastrocnemius muscle nerve nociceptive electrical stimulation was examined in anesthetized, glomectomized, paralyzed, and artificially ventilated cats. (1) In the vagi-intact state, respiratory reflex facilitation was characterized by a sharp rise in peak amplitude, maximum rate of rise or slope, and mean rate of rise of integrated phrenic nerve activity. This was greater during inspiratory phase-locked (T1-locked) muscle nerve electrical stimulation than during expiratory phase-locked (TE-locked) muscle nerve electrical stimulation. "Evoked post-inspiratory phrenic activity" during the early expiratory phase was also observed during TE-locked muscle nerve electrical stimulation. (2) Bilateral vagotomy significantly attenuated the respiratory facilitation during both T1- and TE-locked muscle nerve electrical stimulation. In particular, the "evoked post-inspiratory phrenic activity" during TE-locked muscle nerve electrical stimulation was also attenuated or almost completely abolished. (3) Conditioning electrical stimulation of the vagus nerve revealed facilitatory reflexes which co-exist with inspiratory inhibitory reflexes. (4) The "evoked post-inspiratory phrenic activity" during TE-locked muscle nerve electrical stimulation, which was attenuated or abolished after vagotomy, was restored after vagal T1-locked conditioning stimuli combined with TE-locked muscle nerve electrical stimulation. The results suggest that vagal facilitatory reflexes augment the respiratory reflex facilitation during muscle nociceptive stimulation.

AN ELECTROPHYSIOLOGICAL INVESTIGATION INTO THE PAIN-RELIEVING EFFECTS OF HETEROTOPIC NOCICEPTIVE STIMULI

It has previously been shown that, in normal subjects, heterotopic painful stimuli induce parallel decreases in the sensation of pain and the nociceptive spinal flexion reflex RIII simultaneously evoked by electrical stimulation of the sural nerve. By contrast, heterotopic non-noxious stimuli were ineffective in this respect. In order to assess the possible involvement of supraspinal structures in these changes, we have now compared the effects of nociceptive electrical stimuli applied to the fourth and fifth fingers of the hand on the contralateral RIII reflex in 5 normal subjects and 5 tetraplegic patients suffering from a clinically complete spinal cord transection of traumatic origin. The tetraplegic patient had a C5, C6 or C7 spinal cord transection with lower segments, notably C8 and T1, clinically uninjured. In these patients, sural nerve stimulation induced a biceps femoris reflex which did not differ from the RIII reflex recorded in normal subjects, either in terms of latency or of threshold. In both groups, the RIII reflex threshold was determined and a juxta-threshold RIII reflex was studied before, during and after a 2 min period of conditioning stimulation. The conditioning procedure consisted of nociceptive electrical stimulation applied to the digital branches of the ulnar nerve which arises from C8 and T1, i.e., below the level of the patients' spinal transection. In normal subjects such conditioning elicited painful sensations of 'pin prick', 'burning' and 'squeezing'. It simultaneously induced a strong inhibition of the RIII reflex which outlasted the conditioning period by several minutes. By contrast, non-nociceptive electrical conditioning stimuli (0.1 ms duration pulses of 6 to 8 mA intensity, at 3/s), similarly applied to the digital branches of the ulnar nerve were totally ineffective. In tetraplegic patients not only was the RIII reflex never decreased by the heterotopic nociceptive stimulation but it was, in fact, slightly enhanced. These results show that the effects of heterotopic nociceptive stimulation observed in normal man are possibly mediated by a complex loop involving supraspinal structures. This further underlines the similarity between this phenomenon and the Diffuse Noxious Inhibitory Controls (DNIC) described in the rat, since the latter are observed in intact but not in spinal animals. These findings are discussed with reference to counter-irritation phenomena and procedures aimed at producing analgesia by somatic electrical stimulation.

A study of intracerebroventricular self-administration of leucine or methionine enkephalin by rats in response to intermittent electric shocks

Rats were taught to self-administer Leu-E (10, 25 and 100 μg/μl) or Met-E (0.5, 10 and 100 μg/μl) through a cannula implanted in the lateral cerebral ventricle (i.c.v.). Their self-injection behaviour was studied before, during and after nociceptive stimulation. In the course of the control period of the experiment, the rats rapidly learned lever pressing for self-injection of enkephalin but they did not increase their self-administration of Leu-E or Met-E during the nociceptive electrical stimulation period. Also studied were the acute effect of i.c.v. enkephalin and morphine on tail-flick latency (sec) and electrical threshold vocalization (mA). The analgesic effect of Leu-E and Met-E was of short duration (less than 2–6 min). The mean rise (i.e., analgesia) of the tail-flick threshold showed a significant difference after i.c.v. Met-E only. The acute i.c.v. effect of 20 or 30 μg of morphine induced a long-lasting analgesia, > 40 min. These results show that Leu-E and Met-E are not rewarding during a nociceptive stimulus. This may be due to the short and inconstant analgesic action of i.c.v. enkephalins.

Nociceptive modulation in rats by chemical stimulation of caudate, septum and medial forebrain bundle

The effects of intracerebral microinjections of Thiopental (25 μg) and Metrazol (100 μg) on the defensive motor responses elicited by nociceptive electrical stimulation of the rat's tail were determined. Also, the action of these drugs on the concentration of catecholamines in the injected areas were evaluated by the freeze-drying histofluorescence method. Albino, Holtzman rats implanted with cannulae in the caudate nucleus, medial septal area and medial forebrain bundle were used. The animals were studied following control conditions and after the drug injections. Thiopental show an antinociceptive action when injected into the medial septal area and MFB, and hyperalgesic effect when injected into the caudate nucleus. Metrazol (Pentylenetetrazol) into the medial septal area and caudate nucleus produced hyperalgesia, and analgesia when injected into the MFB. The histochemical study for catecholamines revealed decreases in DA levels in the MFB and caudate nucleus and decreases in the NA in the medial septal area after injections of both drugs. The results are discussed in terms of neuropathways and neurotransmitters involved in nociception.

Changes in adrenocortical function and lipid metabolism during peripheral electrical nociceptive stimulation as a means of studying the antistress action of diazepam and activation of the positive reinforcement system

Experiments on rats showed that the self-stimulation (SS) response reduces the increase in the 11-hydroxycorticosteroid (11-HCS) concentration in blood after electrical nociceptive stimulation (ENS) of the limbs. Diazepam (1 mg/kg) reduced the liberation of 11-HCS and the β-lipoprotein concentration in response to SS and ENS and raised the phospholipid concentration. Diazepam and preliminary ENS evoked activation of SS. It is concluded that diazepam and activation of the positive reinforcement system act in the same direction with respect to 11-HCS excretion and the changes in lipid metabolism during ENS.

Effect of high-frequency peripheral nerve and dorsal column stimulation on neuronal responses in feline nucleus reticularis gigantocellularis after nociceptive electrical stimulation

High-frequency peripheral nerve and dorsal column stimulation have been used clinically to alleviate chronic pain in human patients. However, the mechanisms underlying the analgesic effect of these procedures have not yet been clearly elucidated. The purpose of this investigation was to study the effect of high-frequency dorsal column and peripheral nerve stimulation on neuronal responses in feline nucleus reticularis gigantocellularis after nociceptive stimulation. Whereas dorsal column stimulation had little effect on neuronal responses, high-frequency stimulation of one branch of a divided peripheral nerve typically abolished neuronal responses to stimulation of the other branch of the divided nerve. Similarly, high-frequency stimulation of a contralateral canine tooth pulp abolished the neuronal responses to test stimulation of the ipsilatral canine tooth pulp. Of special significance was the finding that high-frequency stimulation interfered with sensory transmission for periods up to at least 6 hours in duration. These findings have implications for the clinical control of intractable pain and for the role of small-diameter afferents.

The effect of varying stimulus parameters on judgments of nociceptive electrical stimulation.

ABSTRACTThe effect of varying duration and increment of step‐increase of electrical stimulation on the reliability and interjudgment predictability of subjective nociceptive judgments (discomfort, pain, and tolerance) was tested. Differences in mA levels for the nociceptive judgments were consistent but small in comparison to the changes in step and duration. Previous findings related to reliability and predictability were confirmed, and the implications of these findings for the use of electrical stimulation as a pain stimulus are discussed.

Effect of psychotropic drugs on the formation of the avoidance reaction in albino rats to nociceptive electrical stimulation of another animal

Effect of psychotropic drugs on the formation of the avoidance reaction in albino rats to nociceptive electrical stimulation of another animal