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Behavior, pain perception, and the extremely low-birth weight survivor.

This article explores the literature concerning responses to pain of both premature and term-born newborn infants, the evidence for short-term and long-term effects of pain, and behavioral sequelae in individuals who have experienced repeated early pain in neonatal life as they mature. There is no doubt that pain causes stress in babies and this in turn may adversely affect long-term neurodevelopmental outcome. Although there are methods for assessing dimensions of acute reactivity to pain in an experimental setting, there are no very good measures available at the present time that can be used clinically. In the clinical setting repeated or chronic pain is more likely the norm rather than infrequent discrete noxious stimuli of the sort that can be readily studied. The wind-up phenomenon suggests that, exposed to a cascade of procedures as happens with clustering of care in the clinical setting in an attempt to provide periods of rest for stressed babies, an infant may in fact perceive procedures that are not normally viewed as noxious, as pain. Pain exposure during lifesaving intensive medical care of ELBW neonates may also affect subsequent reactivity to pain in the neonatal period, but behavioral differences are probably not likely to be clinically significant in the long term. Prolonged and repeated untreated pain in the newborn period, however, may produce a relatively permanent shift in basal autonomic arousal related to prior NICU pain experience, which may have long-term sequelae. In the long run, the most significant clinical effects of early pain exposure may be on neurodevelopment, contributing to later attention, learning, and behavior problems in these vulnerable children. Although there is considerable evidence to support a variety of adverse effects of early pain, there is less information about the long-term effects of opiates and benzodiazepines on the developing central nervous system. Current evidence reviewed suggests that judicious use of morphine for adjustment to mechanical ventilation may ameliorate the altered autonomic response. It may be very important, however, to distinguish stress from pain. Animal evidence suggests that the neonatal brain is affected differently when exposed to morphine administered in the absence of pain than in the presence of pain. Pain control may be important for many reasons but overuse of morphine or benzodiazepines may have undesirable long-term effects. This is a rapidly evolving area of knowledge of clear relevance to clinical management likely to affect long-term outcomes of high-risk children.

Animals↗

Repeated noxious stimulation of the skin enhances cutaneous pain perception of migraine patients in-between attacks: clinical evidence for continuous sub-threshold increase in membrane excitability of central trigeminovascular neurons.

Recent clinical studies showed that acute migraine attacks are accompanied by increased periorbital and bodily skin sensitivity to touch, heat and cold. Parallel pre-clinical studies showed that the underlying mechanism is sensitization of primary nociceptors and central trigeminovascular neurons. The present study investigates the sensory state of neuronal pathways that mediate skin pain sensation in migraine patients in between attacks. The assessments of sensory perception included (a) mechanical and thermal pain thresholds of the periorbital area, electrical pain threshold of forearm skin, (b) pain scores to phasic supra-threshold stimuli in the same modalities and areas as above, and (c) temporal summation of pain induced by applying noxious tonic heat pain and brief trains of noxious mechanical and electrical pulses to the above skin areas. Thirty-four pain-free migraine patients and 28 age- and gender-matched controls were studied. Patients did not differ from controls in their pain thresholds for heat (44+/-2.6 vs. 44.6+/-1.9 degrees C), and electrical (4.8+/-1.6 vs. 4.3+/-1.6 mA) stimulation, and in their pain scores for supra-threshold phasic stimuli for all modalities. They did, however, differ in their pain threshold for mechanical stimulation, just by one von Frey filament (P=0.01) and in their pain scores of the temporal summation tests. Increased summation of pain was found in migraineurs for repeated mechanical stimuli (delta visual analog scale (VAS) +2.32+/-0.73 in patients vs. +0.16+/-0.83 in controls, P=0.05) and repeated electrical stimuli (delta VAS +3.83+/-1.91 vs -3.79+/-2.31, P=0.01). Increased summation corresponded with more severe clinical parameters of migraine and tended to depend on interval since last migraine attack. The absence of clinically or overt laboratory expressed allodynia suggests that pain pathways are not sensitized in the pain-free migraine patients. Nevertheless, the increased temporal summation, and the slight decrease in mechanical pain thresholds, suggest that central nociceptive neurons do express activation-dependent plasticity. These findings may point to an important pathophysiological change in membrane properties of nociceptive neurons of migraine patients; a change that may hold a key to more effective prophylactic treatment.

Adolescent↗

Pain perception.

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Humans↗

An examination of the effects of isoenergetic intragastric infusions of pure macronutrients on cold pain perception in healthy human volunteers.

Our previous study demonstrated that meals, particularly when rich in fat, significantly reduced the pain induced by the cold pressor stimulus in healthy human subjects. To determine the mechanisms involved, the aim of this study was to bypass the taste and cognitive component of food and to investigate the scope of these analgesic effects with direct intragastric infusion of pure macronutrients in a group of 16 healthy human volunteers (eight male and eight female) on the response to cold-induced pain. All subjects underwent the cold pressor test (CPT) on three occasions in a counterbalanced order: before and after intragastric intubation and infusion of isoenergetic fat (10% intralipid), carbohydrate (CHO-maltodextrin), and a control infusion of isotonic saline. All solutions were of equal volume and administered at room temperature. The CPT was carried out four times on each test day, once before intubation, and 0.5, 1.5, and 2.5 h after intragastric infusion. Radial pulse and blood pressure measurements and visual analogue scales of mood/emotional state were carried out before and after each CPT. There were no significant differences in pain scores between the three test conditions, suggesting that by bypassing the cognitive and taste component of eating, the trigger for any postingestive analgesic effects of food are lost.

Adolescent↗

Sensory and affective aspects of pain perception: is medial thalamus restricted to emotional issues?

Lateral and medial thalamus are traditionally thought to have separate roles in pain processing, with lateral lemniscal regions transmitting discriminative information about location and intensity, while medial nonspecific regions are involved in emotional responses. Contrary to this view, the present study shows that some single neurons in medial thalamus of alert monkey discriminate changes in the intensity of noxious stimuli that are equal to or below the monkey's own discrimination threshold. Since these neurons are also modulated by anesthesia and attentional factors, we suggest that parts of medial thalamus may participate in both discriminative and affective dimensions of pain.

Action Potentials↗

Mechanism of pain in diabetic peripheral neuropathy. Effect of glucose on pain perception in humans.

Animal studies have suggested an altered response to opiate agonists and antagonists as well as an altered pain threshold in diabetic animals. In the studies reported herein, a 50 g glucose infusion in normal subjects resulted in a significant decrease in both the threshold level of pain and the maximal level of pain tolerated, as measured by responses to electrical pain induced by a Grass stimulator. In addition, patients with diabetes mellitus were hyperalgesic when compared with normal subjects. It is concluded that elevated glucose levels and/or rapid fluxes in glucose levels result in a decrease in pain tolerance. These findings have potential clinical implications in the pathophysiology and management of painful diabetic neuropathy and the use of narcotic agents in diabetes mellitus.

Adult↗

Gender role expectations of pain: relationship to experimental pain perception.

The primary purpose of this study was to investigate the influence of an individual's Gender Role Expectations of Pain (GREP) on experimental pain report. One hundred and forty-eight subjects (87 females and 61 males) subjects underwent thermal testing and were asked to report pain threshold, pain tolerance, VAS ratings of pain intensity and unpleasantness, and a computerized visual analogue scales (VAS) rating of pain intensity during the procedure. Subjects completed the GREP questionnaire to assess sex-related stereotypic attributions of pain sensitivity, pain endurance, and willingness to report pain. Consistent with previous research, significant sex differences emerged for measures of pain threshold, pain tolerance, and pain unpleasantness. After statistically controlling for age, GREP scores were significant predictors of threshold, tolerance, and pain unpleasantness, accounting for an additional 7, 11, and 21% of the variance, respectively. Sex remained a significant predictor of pain tolerance in hierarchical regression analyses after controlling for GREP scores. Results provide support for two competing but not mutually exclusive hypotheses related to the sex differences in experimental pain. Both psychosocial factors and first-order, biological sex differences remain as viable explanations for differences in experimental pain report between the sexes. It appears that GREP do play a part in determining an individual's pain report and may be contributing to the sex differences in the laboratory setting.

Adolescent↗

The dual-system hypothesis of pain perception.

We describe a dual-system hypothesis relating the seemingly contradictory findings reported in clinical and experimental investigations of pain. This incorporates a model in which two neuronal systems are related, involving Substance P (SP) and Enkephalin (E). This model uses feedback loops holding the systems in balance. The analogy to a control system is also made.

Animals↗

Impact of age, gender and cognitive functioning on pain perception.

BACKGROUND: Experimental data on nociception in the elderly have so far been contradictory and most of these have been obtained using psychophysical methods with little attention paid simultaneously to the state of cognition and the psychometric performance of the subjects. OBJECTIVE: The aim of this study was twofold: (1) to evaluate the impact of age on experimental nociception thresholds, and (2) to investigate the interactions of age, sex, cognition and psychometric performance with nociception thresholds. METHODOLOGY: (1) Two groups, one young and one elderly, of 42 healthy participants each, 21 males and 21 females, were compared as regards nociception thresholds with thermal and mechanical stimuli (heat and pressure detection and tolerance thresholds). (2) The elderly group took cognitive (mini-mental test), psychometric (choice reaction time) and psychophysical tests in auditory (sensibility, tolerance, discrimination) and nociceptive fields. RESULTS: This study shows that (1) pressure nociception decreases with age especially in males, while thermal thresholds are not modified, and (2) correlations exist between cognitive function, psychometric performance, tolerance to loud sounds and tolerance to mechanical noxious stimuli. CONCLUSION: Our results suggest that cognitive and psychomotor parameters have to be taken into account when assessing experimental nociception in the elderly. Further studies are needed to evaluate possible report biases and to assess these interactions in old patients with pain and in mildly sensory, cognitive or motor impaired elderly subjects.

Adult↗

Rhythmic variations in pain perception in osteoarthritis of the knee.

Twenty patients with primary osteoarthritis (OA) of the knee completed self-administered questionnaires probing pain severity on 10 occasions every day for 7 consecutive days. Rhythmometric analyses detected a significant circadian rhythm in pain in the majority of patients. Our data suggest that perceived pain severity varies substantially with time of day. These observations have important implications for the administration of pain questionnaires as outcome measures for clinical trials of nonsteroidal antiinflammatory drugs in OA of the knee.

Aged↗

Molecular basis for the perception of pain.

It is perhaps presumptuous to talk about the molecular basis of a subjective sensation such as pain, but defined conformational changes in membrane proteins, controlled by a family of extra- and intracellular messenger molecules, are known to underlie the activation of sensory nerve terminals and the process of synaptic neurotransmission, which are necessary for pain perception. Furthermore, a subset of neurotransmission processes has a permissive, and possibly exclusive, role in pain perception. Clearly, the experience of pain in the clinical sense with all its affective components of unpleasantness and suffering cannot yet be fully understood in molecular terms, but the process of nociception, whereby the signal generated as a result of tissue damaging or potentially damaging peripheral stimuli reaches and evokes neuronal activity in the central nervous system, is becoming better characterized. Recent advances in neurobiology have given us insights that are already helping improve understanding of the events that lead to a patient experiencing pain and, it is hoped, will also lead to more successful treatment strategies.

Animals↗