Diffuse Noxious Inhibitory Controls Research Articles

Pain additivity, diffuse noxious inhibitory controls, and attention: A functional measurement analysis

This study utilized the methodology of Functional Measurement theory to investigate the additivity of painful and non-painful thermally induced experiences at one body site with those produced by brief noxious and innocuous electrical stimuli at another. Forty healthy young subjects were tested, using a Peltier thermode to induce tonic pain and an electrocutaneous stimulator for presenting phasic pain, under conditions of either full attention or visual/cognitive distraction (counting numerous light signals) in order to evaluate whether the summed effects are attributable to refocused attention. Six levels of intensity were combined in a factorial design for both tonic and phasic pain. Subjects indicated the overall strength of their dual perception on a visual analog scale. Stimuli showed complex patterns of interaction. Two stimuli were generally rated as greater than one, but the summation was far from additive and greatly influenced by the intensity of the stronger stimulus, suggesting inhibitory action. In general, tonic heat pain strongly affected the perception of phasic electrocutaneous pain whereas the reverse was only partly true. Distraction had a very small effect, suggesting that the “pain inhibits pain” phenomenon attributable to diffuse noxious inhibitory controls (DNIC) is not due to attentional processes. Our data also relate to issues regarding spatial summation across dermatomes and to adaptation level effects in pain, in which a strong painful experience serves as an anchor or comparison point by which others are judged. The psychophysical findings provide a perceptual foundation for clinical phenomena in which patients face with comorbid pain disorders.

Evidence of diffuse noxious inhibitory controls (DNIC) elicited by cold noxious stimulation in patients with provoked vestibulodynia

Provoked vestibulodynia is a common cause of superficial dyspareunia in young women. Recent evidence has pointed out the importance of studying endogenous pain modulation in these women. An impairment of diffuse noxious inhibitory controls (DNIC) has been suggested in chronic pain conditions with a female predominance such as fibromyalgia and temporomandibular disorder. Our aim was to examine whether patients with provoked vestibulodynia and healthy women with or without combined oral contraceptives (COC) display a DNIC response to cold noxious stimulation. Twenty patients with provoked vestibulodynia not using COC, 20 healthy women on COC and 20 healthy women without COC were included and tested days 7–11 of their menstrual cycle. Pressure pain thresholds (PPTs) and pain ratings using VAS were measured on the arm and leg before and during a cold pressor test. A socio-medical questionnaire, the Hospital and Anxiety Depression Scale and the Short Form-36 were completed. The majority of the subjects in all three study groups significantly increased their PPTs during cold noxious stimulation indicating a DNIC response. The patients displayed lower PPTs compared to the healthy women. Depression, anxiety and bodily pain were more often reported by the patients. No differences related to the intake of COC were observed between the healthy women. In conclusion, women with provoked vestibulodynia as well as healthy women irrespective of COC status display a DNIC response indicating an endogenous pain inhibition. However, the results imply a systemic hypersensitivity in women with vestibulodynia with low general pain thresholds as compared to healthy women.

Mechanisms of Action of Acupuncture for Chronic Pain Relief – Polymodal Receptors Are the Key Candidates

Therapeutic benefits of acupuncture for chronic pain patients have been clearly identified in recent clinical trials. Underlying mechanisms of acupuncture action mediated by endogenous opioids have been well demonstrated. The existence of pain inhibitory systems in the central nervous system has also been clarified and acupuncture seems to be a potent stimulus for activating the analgesic systems, although the pain mechanisms in acute and chronic states are essentially different. On the other hand, the exact nature of the acupuncture point still remains unclear. Here, we propose a key role of polymodal receptors (PMR) in acupuncture and moxibustion and offer a rational explanation of the acupuncture point as a sensitised PMR. Moxibustion (burning of moxa) therapy has been shown by medical historians to predate the use of acupuncture, and the meridian theory developed in association with moxibustion treatment. A variety of sensory receptors are activated by acupuncture and/or moxibustion, but there are very few that can be excited by both stimuli. PMRs are one of the most promising candidates. The functional characteristics of PMRs correspond with those of acupuncture action in the periphery; and tender or trigger points, one of the primitive features of acupuncture points, are assumed to be the sites of sensitised PMRs. Diffuse noxious inhibitory control (DNIC) is proposed as a possible mechanism of immediate action of acupuncture, and inputs for the development of DNIC seem to be the PMRs. In our experimental model, repeated eccentric contractions of muscle produced local tenderness at the palpable band and induced a typical referred pain pattern on application of pressure. Repeated indomethacin injections inhibited the production of the experimental trigger point. These lines of evidence suggest that the acupuncture points are the sites where the PMRs are sensitised and that such conditions might be repeatedly produced by various biomechanical stressors, insufficient blood supply and metabolic products.

When It's Hard To Breathe, Maybe Pain Doesn't Matter. Focus on “Dyspnea as a Noxious Sensation: Inspiratory Threshold Loading May Trigger Diffuse Noxious Inhibitory Controls in Humans”

Dyspnea (shortness of breath) and pain are well-evolved warnings of important physiological derangements that may require animals to alter their behavior to survive. Dyspnea and pain are also two of the most common symptoms that bring patients to medical care, another potentially adaptive behavior.

A background to acupuncture and its use in chronic painful musculoskeletal conditions

This article gives a brief description of the origins of acupuncture and describes some of the underlying philosophy behind this treatment and attempts to place it in context of the traditional Chinese medicine genre within which acupuncture is set. The article then explains the difference between traditional and Western style acupuncture and explains how point selection is made. The use of acupuncture is steadily increasing for a variety of reasons, it is a very safe intervention particularly when compared to conventional treatment and its lack of serious side effects might in part account for some of its popularity. The science behind acupuncture is also explored in terms of its underlying mechanisms and includes pain gate, endogenous opioids, diffuse noxious inhibitory control, serotonin and bioelectricity as possible explanations. The efficacy of acupuncture for a range of chronic musculoskeletal conditions is then explored and it is concluded that acupuncture has a place in the treatment of chronic musculoskeletal pain and in particular osteo-arthritis (OA). Where degenerative conditions are involved, acupuncture clearly cannot provide a 'cure' but can provide symptomatic relief, often over a prolonged period.

268 INTENSITY MODULATION OF CUTANEOUS ELECTRICAL STIMULATION: EPS AND SUBJECTIVE RATINGS

Chronic pain research is increasingly focused on the neuroplastic mechanisms underlying subjective pain experience. The latter is often measured using reported pain intensity, e.g. using a numeric rating scale (NRS). Evoked Potentials (EPs) reflect the cortical representation of applied stimuli and are experimentally used for observation of neural processing. Both sensation and cortical representation depend on central modulation of applied stimuli, as described by theories like Diffuse Noxious Inhibitory Control and the Gate Control Theory. In multiple mechanisms both tactile and nociceptive activations interact, indicating that the distribution of activated afferents (Aβ, Aδ-fibers) is relevant for correct interpretation of results. From this point of view, the traditional use of amplitude modulated single electrical stimulation pulses (SP) might not be optimal for studying central processing of pain as the amplitude changes this distribution (depending on the local fiber densities). Pulse trains (PT) with a variable number of fixed amplitude pulses might be more appropriate stimuli as they resemble the coding of stimulus intensity by skin receptors. In this study we therefore compared NRS scores and EP components (P90, N150, P200, P300) obtained with SP and PT modulated intensity (I). A total of 30 healthy female subjects were electrically stimulated at the tip of the left middle finger or forearm. NRS scores and EPs were averaged from 105 randomized stimuli at 5 intensity levels. Both the I-EP (components) and the I-NRS relationships differed depending on the modulation method and stimulation site. Although the repeatedly reported NRS-EP correlation was reproduced for SP at the finger, no significant correlation was found with stimulation at the forearm. For PT however, the NRS-EP correlation was found for both stimulation sites. These findings support the view that SP and PT methods offer a different excitation of neural mechanisms, which might be fruitful for future observation of central mechanisms underlying chronification of pain.

Dyspnea as a Noxious Sensation: Inspiratory Threshold Loading May Trigger Diffuse Noxious Inhibitory Controls in Humans

Dyspnea, a leading respiratory symptom, shares many clinical, physiological, and psychological features with pain. Both activate similar brain areas. The neural mechanisms of dyspnea are less well described than those of pain. The present research tested the hypothesis of common pathways between the two sensations. Six healthy men (age 30-40 yr) were studied. The spinal nociceptive flexion reflex (RIII) was first established in response to electrical sural stimulation. Dyspnea was then induced through inspiratory threshold loading, forcing the subjects to develop 70% of their maximal inspiratory pressure to inhale. This led to progressive inhibition of the RIII reflex that reached 50 +/- 12% during the fifth minute of loading (P < 0.001), was correlated to the intensity of the self-evaluated respiratory discomfort, and had recovered 5 min after removal of the load. The myotatic H-reflex was not inhibited by inspiratory loading, arguing against postsynaptic alpha motoneuron inhibition. Dyspnea, like pain, thus induced counterirritation, possibly indicating a C-fiber stimulation and activation of diffuse noxious inhibitory descending controls known to project onto spinal dorsal horn wide dynamic range neurons. This confirms the noxious nature of certain types of breathlessness, thus opening new physiological and perhaps therapeutic perspectives.

GABAergic modulation of diffuse noxious inhibitory controls (DNIC): a test by use of lorazepam

Diffuse noxious inhibitory controls (DNIC) are an important supra-spinal mechanism of pain inhibition. Neurotransmitters and modulators involved in DNIC are serotonin and endogenous opioids. The influence of substances binding to the GABA(A) receptor complex, which has been suggested to play an important role in descending pain inhibition on DNIC has not yet been investigated. The aim of the present study was to find out whether the inhibitory action of DNIC might also be mediated by GABAergic mechanisms. Therefore, DNIC modulation via GABAergic mechanisms was studied in a double blind, placebo-controlled crossover design by oral application of 0.02 mg/kg(body weight )lorazepam in 20 healthy subjects. DNIC inhibition was induced by heterotopically administered tonic heat. The inhibitory effect was assessed by use of a multiple staircase method, measuring electrocutaneous detection, and pain thresholds in parallel. Concurrent tonic heat stimuli, at both painful and non-painful levels, significantly increased the electrical pain threshold whereas the electrical detection threshold was not affected. This pain-specific inhibitory effect did not differ significantly between sessions with lorazepam and placebo. Accordingly, lorazepam did not modify the inhibitory action of DNIC although lorazepam generally increased heat pain threshold. The results of the present study provided no evidence for DNIC being mediated by activation of the GABA(A) receptor complex.

Abnormal Modulatory Influence of Diffuse Noxious Inhibitory Controls in Migraine and Chronic Tension-Type Headache Patients

The aim of this study was to evaluate the function of pain modulating systems subserving diffuse noxious inhibitory controls (DNICs) in primary headaches. DNICs were examined in 24 migraineurs, 17 patients with chronic tension-type headache (CTTH) and 20 healthy subjects by means of nociceptive flexion RIII reflex and the cold pressor test (CPT) as heterotopic noxious conditioning stimulation (HNCS). The subjective pain thresholds (Tp) and the RIII reflex threshold (Tr) were significantly lower in CTTH vs. controls. In controls a significant inhibition of the RIII reflex was observed during the CPT (-30%, P < 0.05). Conversely, migraine and CTTH patients showed facilitation (+31%, P < 0.05 and +40%, P < 0.01, respectively) of the RIII reflex during the HNCS. This study demonstrates a dysfunction in systems subserving DNICs in both migraine and CTTH. Impairment of endogenous supraspinal pain modulation systems may contribute to the development and/or maintenance of central sensitization in primary headaches.

Endogenous pain inhibitory systems activated by spatial summation are opioid-mediated

We previously developed a spatial summation model and demonstrated that spatial summation of pain involves the activation of both excitatory and inhibitory systems. The aim of this study was to determine whether the endogenous pain inhibitory systems recruited by the spatial summation model are opioid-mediated by verifying if they could be blocked by the opioid antagonist naloxone. Twenty healthy volunteers (10 men, 10 women) participated in a randomized, four-session, cross-over study. Each session consisted of pain perception ratings (visual analog scale) taken during the immersion of different surfaces of the arm in circulating noxious cold water (12 °C). The arm was arbitrarily divided into eight segments from fingertips to shoulder. Two sessions were increasing (from fingertips to shoulder) and two sessions were decreasing (from shoulder to fingertips). All sessions consisted of eight consecutive 2-min immersions separated by 5-min resting periods. Intravenous injections of naloxone hydrochloride (0.14 mg/kg) or saline (NaCl, 0.9%) were administered under double-blind conditions. We found that during the control session (saline injection) there was a significant difference in pain intensity ratings between the increasing and decreasing sessions. The decreasing session resulted in lower pain intensity. As previously demonstrated, this lowering of the perception curve seems to be due to a large recruitment of inhibitory systems at the beginning of the decreasing session as opposed to a gradual recruitment during the increasing session. However, during the opioid inhibition session (naloxone injection) no differences were found between the increasing and decreasing sessions. Naloxone inhibited the endogenous pain inhibitory systems activated by the spatial summation model, suggesting that these systems have an opioid-mediated component, as previously reported for diffuse noxious inhibitory controls.

(703): Diffuse noxious inhibitory controls: Abnormal pain modulation in chronic pain patients

(703): Diffuse noxious inhibitory controls: Abnormal pain modulation in chronic pain patients

Functional Abdominal Pain Syndrome

Functional abdominal pain syndrome (FAPS) differs from the other functional bowel disorders; it is less common, symptoms largely are unrelated to food intake and defecation, and it has higher comorbidity with psychiatric disorders. The etiology and pathophysiology are incompletely understood. Because FAPS likely represents a heterogeneous group of disorders, peripheral neuropathic pain mechanisms, alterations in endogenous pain modulation systems, or both may be involved in any one patient. The diagnosis of FAPS is made on the basis of positive symptom criteria and a longstanding history of symptoms; in the absence of alarm symptoms, an extensive diagnostic evaluation is not required. Management is based on a therapeutic physician-patient relationship and empirical treatment algorithms using various classes of centrally acting drugs, including antidepressants and anticonvulsants. The choice, dose, and combination of drugs are influenced by psychiatric comorbidities. Psychological treatment options include psychotherapy, relaxation techniques, and hypnosis. Refractory FAPS patients may benefit from a multidisciplinary pain clinic approach.

Impairment of pain inhibition in chronic tension-type headache

Evidence has been accumulated suggesting that a dysfunction in pain inhibitory systems, i.e. in ‘diffuse noxious inhibitory controls‘ (DNIC)-like mechanisms, might be—amongst other factors—responsible for the development of anatomically generalized chronic pain like fibromyalgia. The aim of the present study was to look for similar impairments in chronic tension-type headache (CTTH) as a regionally specific pain syndrome. Twenty-nine CTTH patients and 25 age- and sex-matched healthy control subjects participated in the study. After baseline assessment of electrical detection and pain thresholds, tonic heat stimuli were concurrently applied by a thermode to the thigh to induce DNIC-like pain inhibition. Tonic heat stimuli were applied either slightly above (‘pain’ condition) or slightly below (‘heat’ condition) pain threshold. For determination of electrical detection and pain thresholds, electrocutaneous stimuli were administered either to the forearm (extra-cranial site) or to the temple (cranial site), using a multiple staircase procedure. The increase in the electrical detection and pain thresholds induced by concurrent tonic heat stimulation was significantly smaller in the CTTH patients than in the control subjects. This group difference was present during the ‘pain’ as well as the ‘heat’ condition. Furthermore, the electrical detection and pain thresholds were affected in this group-specific manner both at the forearm and at the temple. These findings suggest that patients with CTTH suffer from deficient DNIC-like pain inhibitory mechanisms in a similar manner, as do patients with anatomically generalized chronic pain like fibromyalgia.

Measuring Minimum Alveolar Concentration

Measuring Minimum Alveolar Concentration

Heterotopic ischemic pain attenuates somatosensory evoked potentials induced by electrical tooth stimulation: Diffuse noxious inhibitory controls in the trigeminal nerve territory

The purpose of this study was to determine whether the late component of somatosensory evoked potentials (SEP) induced by electrical tooth stimulation and pain intensity are inhibited by heterotopic ischemic stimulation. The tourniquet pressure with 50 mmHg greater than the individual’s systolic pressure was applied to the left upper arm for 10 min as ischemic conditioning stimulation. The late component of SEP and visual analogue scale (VAS) were recorded at 4 times and both were significantly decreased when ischemic conditioning stimulation was applied. The maximum reductions in SEP amplitude and the VAS value were 26.1% and 21.2%, respectively, during ischemic conditioning stimulation. After-effect was observed 5 min after removal of the conditioning stimulation. The present study revealed that heterotopic ischemic stimulation attenuated the late component of SEP induced by electrical tooth stimulation, triggering diffuse noxious inhibitory controls (DNIC) and after-effects in the trigeminal nerve territory. It was also suggested that the DNIC effect differs, depending on the intensity, kind, and quality of the test and conditioning stimuli.

Neurophysiological approach to central pain modulation in primary headaches

The study of CNS painmodulating pathways has led to important discoveries about the role of central nociceptive structures such as PAG and hypothalamus in the pathophysiology of episodic and chronic primary headaches. Functional neuroimaging studies have revealed that primary headaches are characterised by different patterns of activation of central pain modulatory structures. A future model of headache pathophysiology investigating the contribution of CNS pain–modulating pathways will probably increase our understanding of pain processing in primary headaches. Herein we review the neurophysiological approaches to assess central pain modulation in primary headaches with emphasis on the diffuse noxious inhibitory control, a form of endogenous pain inhibition. In addition, patients’ data will be presented that highlights the utility of such methods for primary headache’s pathophysiology and clinical monitoring.

Lack of sex differences in modulation of experimental intraoral pain by diffuse noxious inhibitory controls (DNIC)

The aims of this study were to investigate possible sex differences in (a) intraoral pain evoked by topical application of capsaicin to the gingiva, and (b) the modulation of this pain by diffuse noxious inhibitory controls (DNIC). Three groups with a total of fifty-four healthy volunteers (20 men, 20 women using oral contraceptives (W+OC), 14 women not using (W−OC)) completed the study. In two sessions, intraoral pain was evoked by topical application of 30 μL 5% capsaicin to the gingiva. Conditioning stimuli were applied with three min hand immersion in ice water in one session and 30 °C water (control) in another session. The capsaicin-evoked pain and the water-evoked pain were evaluated by the participants on visual analogue scales (VAS). No main effects of group in capsaicin-evoked pain ( P>0.062) or water-evoked pain ( P>0.149) were found. There was a significant group x time interaction ( P<0.001) with W+OC reporting lower capsaicin-evoked pain scores than W−OC in the early phase (2–3 min) and lower pain scores than men in the later phase (5–11 min). The degree of modulation by DNIC did not differ between groups ( P=0.636). In conclusion, for a superficial type of intraoral pain, only minor sex differences were found in pain intensity and no differences in the degree of endogenous modulation by DNIC. Female sex and the use of OC may not consistently be associated with higher sensitivity to pain.

Time dependant differences in pain sensitivity during unilateral ischemic pain provocation in healthy volunteers

Plurisegmental endogenous pain inhibitory mechanisms related to diffuse noxious inhibitory controls (DNIC) were demonstrated in animal experiments to act on multireceptive neurons of the entire cord outside the conditioned segment without any side differences. Human experiments have demonstrated altered pain sensitivity to pressure, heat and electrical stimulation during heterotopic noxious conditioning stimulation (HNCS). The purpose of the study was to examine if side and/or time differences in pain thresholds and suprathreshold pain sensitivity for pressure and heat, respectively, could be detected during HNCS. Perception thresholds to pressure and heat pain as well as the sensitivity to suprathreshold pressure (SPP) and heat pain (SHP) were assessed in 18 healthy volunteers bilaterally at the thighs before, during and following ischemia-induced pain of the left forearm (HNCS). The assessments started with either the right (10 subjects) or the left thigh (8 subjects). During HNCS the pressure pain threshold increased significantly ( p < 0.001) on both sides alike. No significant difference in the magnitude of the altered pressure pain threshold was seen between sides for the first or the lastly assessed side. On the lastly assessed side only SPP and SHP increased significantly on both sides alike ( p < 0.02 and p < 0.03, respectively), without magnitude differences between sides. During unilateral HNCS of the left arm, a time factor was demonstrated only for alterations in suprathreshold pain sensitivity, without any differences in magnitude between sides. Therefore, the results have implications for future design of HNCS-related experimental and clinical studies.

Central pain control

We describe the anatomic and physiological components involved in pain physiology, with the goal of providing readers with the background information needed to understand central pain control mechanisms. These include spinal segmental controls, supraspinal excitatory and inhibitory controls, and diffuse noxious inhibitory controls (DNICs). Pain is a subjective sensation produced by an emotionally unpleasant experience considered to originate in adaptive processes taking place within neuron networks located at various levels of the central nervous system. The intensity of the components of pain is influenced by the stimulus characteristics, patient-related factors, and the setting in which the stimulus occurs. The various components of pain and the psychological and neurophysiological mechanisms that underlie the affective dimension of pain are reviewed. As a conclusion, phantom pain is used to illustrate the role for physiological systems independent from those involved in the physiology of nociception and pain, such as the motor cortex. This example highlights the extreme complexity of pain and pain control systems in humans.

Le contrôle central de la douleur

We describe the anatomic and physiological components involved in pain physiology, with the goal of providing readers with the background information needed to understand central pain control mechanisms. These include spinal segmental controls, supraspinal excitatory and inhibitory controls, and diffuse noxious inhibitory controls. Pain is a subjective sensation produced by an emotionally unpleasant experience considered to originate in adaptive processes taking place within neuron networks located at various levels of the central nervous system. The intensity of the components of pain is influenced by the stimulus characteristics, patient-related factors, and the setting in which the stimulus occurs. The various components of pain and the psychological and neurophysiological mechanisms that underlie the affective dimension of pain are reviewed. As a conclusion, phantom pain is used to illustrate the role for physiological systems independent from those involved in the physiology of nociception and pain, such as the motor cortex. This example highlights the extreme complexity of pain and pain control systems in humans.