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PubMed1995

Gender differences in pain ratings and pupil reactions to painful pressure stimuli.

In order to investigate gender differences in pain perception, the present study employed both a psychophysical and a psychophysiological measure. In experiment 1, 20 subjects rated the painfulness of 4 different levels of tonic pressure applied to their fingers using a verbally anchored categorization procedure. In general agreement with studies of pain threshold and tolerance, female subjects reported greater pain at high levels of stimulation, with no gender difference being evident at low pressure levels. In experiment 2, 16 different subjects were exposed to the same painful pressure stimuli while measuring their pupil reactions using infrared video pupillometry. The pupil dilations seen during the last 10 sec of the 20-sec pressure application turned out to be a highly significant indicator of pain intensity. When female and male subjects were compared on this measure, a similar divergent pattern as in the psychophysical data emerged, with female subjects showing greater pupil dilations at high pressure levels only. The fact that gender differences in pain perception can be demonstrated using an autonomic indicator of pain that is beyond voluntary control suggests that these differences reflect low-level sensory and/or affective components of pain rather than attitudinal or response-bias factors.

Female↗
PubMed1994

Heterotopic nociceptive conditioning stimuli and mental task modulate differently the perception and physiological correlates of short CO2 laser stimuli.

The present study was aimed at examining the specificity of the action of heterotopic nociceptive conditioning stimulation (HNCS) by comparing its effects of those induced by a mental task (MT). Five test stimuli made from short CO2 laser pulses (duration: 40 msec; diameter: 10 mm; intensity: 0.25-0.8 Joules) were delivered every 30 to 45 sec at random to 4 different spots on the skin of the upper lip in 3 groups of 10 healthy subjects. The two most intense stimuli were perceived as painful, the two least intense stimuli as warm, and the intermediate stimulus as hot or near painful. Perception (VAS), reaction time (T) and cerebral evoked potentials (CEPs) were monitored before, during and after conditioning stimulation consisting either of HNCS (hand submerged in cold water) or of MT (arithmetic subtraction). Pain perception (first pain) threshold was increased in both conditioning stimulations; however, the stimulus-response curve and the neurophysiological correlates were differently affected. During HNCS, the stimulus-response curve was depressed and T was increased mainly for the intermediate stimulus, whilst CEP power density was reduced for all stimulus intensities; discrimination performance near pain threshold was dramatically depressed. During MT, the stimulus-response curve was shifted down toward higher stimulus intensities, T was equally increased for all stimulus intensities, whereas CEP power density was not changed; discrimination performance remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Endogenous opiates increase pain tolerance after stress in humans.

This study investigates the role of endogenous opioids in the regulation of pain in humans. Two groups of healthy volunteers were subjected to different stress situations (cold pressor and arithmetic). In a double-blind design the changes in pain tolerance after stress were measured after an injection of either 0.8 mg naloxone or placebo. The cold pressor test raised the pain threshold in the placebo-treated group, but not in the naloxone-treated group. Mental arithmetic had no effect on pain perception. One can conclude therefore that physical stress may change pain perception depending upon the secretion of endogenous opioids.

Adult↗
PubMed1976

[On the mechanism of action of acupuncture analgesia (author's transl)].

The correlation between the effects of acupuncture (A) and hypnosuggestion (H) on subjective pain perception was studied in normal volunteers using somatosensory evoked potentials technique. Both methods influenced identically the subjective pain perception and affected the evoked cortical responses similarly. In those subjects in whom analgesia was achieved, location of the A needles proved unimportant and the suppression of the cortical response elicited by A or H was identical. This could be explained by cortically induced inhibitory activity in descending control systems for both methods. A. analgesia thus appears to be a suggestive modality which depends on individual susceptibility. A specific cultural background also seems to be of importance.

Acupuncture Therapy↗
PubMed1989

Depression, pain, and hemispheric activation.

The present study attempts to delineate the role of hemispheric activation in depression and pain. It was hypothesized that the right hemisphere is specialized to become activated by and to process negative affective stimuli, and that this specialization may play a role in the co-occurrence of depression and pain. The relationship between depression, experimental pain, and cerebral laterality was investigated in 16 depressed and 16 nondepressed, right-handed, female students. Cerebral laterality was measured via tasks assessing visual and auditory biases, and pain was assessed via a cold pressor task. The proposition that the right hemisphere mediates the co-occurrence of pain and depression was not supported, but specific findings did suggest that the right hemisphere may play a unique role in pain perception. Data from the visual task indicated that prior exposure to pain results in increased right hemisphere activation as indicated by a left visual field bias. Pain perception was a complex function of mood, preceding tasks, and the hand tested, and it was suggested that exposure to a typical right-hemisphere task increased the left side lateralization of pain in nondepressed subjects. Implications of these findings are discussed for coexisting problems of pain and depression and for the lateralization of pain in disorders judged to involve a significant psychogenic component.

Adolescent↗
PubMed2003

Family members' perceptions of pain and distress related to analgesics and psychotropic drugs, and quality of care of elderly nursing home residents.

The aims of the present study were: (1) to describe family members' perceptions of nursing homes residents' pain and distress in relation to analgesics and psychotropic drugs; and (2) to compare whether background variables, dementia, help/support, prescribing of analgesics and psychotropic drugs, and quality of care vary between subgroups of residents. Two hundred and thirty-two family members of elderly people in 10 Swedish nursing homes participated in the study. The participants responded to a questionnaire including background variables, pain and distress variables, and the Quality from the Patient's Perspective (QPP) questionnaire. Data on drug prescribing was obtained from the medical records. The head nurse on each ward noted whether or not the resident had a documented or known diagnosis of dementia. The results showed that a high frequency of elderly nursing home residents were estimated as having physical pain and worry. A large number of the residents were prescribed psychotropic drugs. In addition, some of the residents with moderate or severe physical pain were not prescribed any analgesics. The residents were divided into three subgroups based on scores of physical discomfort, physical pain and worry. Subgroup comparisons differed with regard to sex, help/support, drugs and quality of care. Staff have a responsibility to assess the residents' pain and distress since this will form a basis for better pain and distress management. Other suggestions for improving quality of care are the provision of better information to the family members and the residents, meaningful occupation, less task-oriented care, and care that involves residents.

Aged↗
PubMed2006

Acoustic noise in functional magnetic resonance imaging reduces pain unpleasantness ratings.

Functional magnetic resonance imaging (fMRI) is increasingly used in cognitive studies. Unfortunately, the scanner produces acoustic noise during the image acquisition process. Interference from acoustic noise is known to affect auditory, visual and motor processing, raising the possibility that acoustic interference may also modulate processing of other sensory modalities such as pain. With the increasing use of fMRI in the investigation of the mechanisms of pain perception, particularly in relation to attention, this issue has become highly relevant. Pain is a complex experience, composed of sensory-discriminative, affective-motivational and cognitive-evaluative components. The aim of this experiment was to assess the effect of MRI scanner noise, compared to white noise, on the affective (unpleasantness) and the sensory-discriminative (localisation) components of pain. Painful radiant heat from a CO(2) laser was delivered to the skin of the right forearm in 24 healthy volunteers. The volunteers attended to either pain location or pain unpleasantness during three conditions: i) no noise, ii) exposure to MRI scanner noise (85 dB) or iii) exposure to white noise (85 dB). Both MRI scanner noise and white noise significantly reduced unpleasantness ratings (from 5.1 +/- 1.6 in the control condition to 4.7 +/- 1.5 (P = 0.002) and 4.6 +/- 1.6 (P < 0.001) with scanner and white noise respectively), whereas the ability to localise pain was not significantly affected (from 85.4 +/- 9.2% correct in the control condition to 83.1 +/- 10.3% (P = 0.06) and 83.9 +/- 9.5% (P = 0.27) with MRI scanner and white noise respectively). This phenomenon should be taken into account in the design of fMRI studies into human pain perception.

Acoustic Stimulation↗
PubMed2001

Representation of acute and persistent pain in the human CNS: potential implications for chemical intolerance.

The study of pain may be relevant to the study of chemical intolerance (CI) in many ways. Pain is often reported as a symptom of CI and it is defined as a subjective experience similar to many other symptoms of CI, making its objectification difficult. Furthermore, the CNS plastic changes that underlie the development of persistent pain states and abnormal pain responses may share some similarities with those involved in the sensitization to environmental chemicals. Functional brain imaging studies in humans demonstrate that acute pain evoked by nociceptive stimulation is accompanied by the activation of a widely distributed network of cerebral structures, including the thalamus and the somatosensory, insular, and anterior cingulate cortices. Abnormal activity within these regions has been associated with the experience of pain following damage to the peripheral or central nervous system (neuropathic pain) in a number of clinical populations. In normal individuals, activity within this network is correlated with subjective pain perception, is highly modifiable by cognitive interventions such as hypnosis and attention, and has been associated with emotions. Other cognitive mediators such as expectations can also produce robust changes in pain perception (e.g., in placebo analgesia). These effects likely depend on both higher-order cerebral structures and descending mechanisms modulating spinal nociceptive activity. These psychological processes can be solicited to reduce clinical pain and we speculate that they may further attenuate or promote central mechanisms involved in the transition from acute to persistent pain states. The investigation of central determinants of subjective experience is essential to assess the possibility that higher-order brain/psychological processes modulate and/or mediate the development of persistent pain states. These factors may contribute to the development of symptoms in CI.

Acute Disease↗
PubMed2001

Somatosensory event-related potential and autonomic activity to varying pain reduction cognitive strategies in hypnosis.

OBJECTIVES: The issues of differential effects among cognitive strategies during hypnosis in the control of human pain are under active debate. This study, which employs measures of pain perception, electrocortical and autonomic responses, was aimed at determining these pain-related modulations. METHODS: Somatosensory event-related potentials (SERPs) to noxious stimuli under an odd-ball paradigm were recorded at the frontal, temporal and parietal regions in 10 high, 9 mid, and 10 low hypnotizable right-handed young women, at waking baseline, varying cognitive strategies (deep relaxation, dissociative imagery, focused analgesia) in hypnosis and placebo conditions. The phasic heart rate (HR) and skin conductance response were also recorded. The analysis was focused on the frequent standard trials of the odd-ball SERPs. Repeated measures analysis of variance was conducted to examine the experimental effects. RESULTS: Focused analgesia induced the largest reduction in pain rating, more in the high than low hypnotizable subjects. In high hypnotizable subjects, the N2 amplitude was greater over frontal and temporal scalp sites than over parietal and central sites, whereas in moderately and low hypnotizable subjects, N2 was greater over temporal sites than over frontal, parietal, and central sites. These subjects also displayed a larger N2 peak over temporal sites during focused analgesia than in the other conditions. The P3 amplitude was smaller under deep relaxation, dissociative imagery and focused analgesia in the high hypnotizable subjects. For these subjects, the smallest P3 peaks were obtained for dissociated imagery and focused analgesia over frontal and temporal sites. In contrast, for the P3 peak, low hypnotizable subjects failed to show significant condition effects. In all of the subjects, the skin conductance and HR were smaller during hypnotic suggestions than in the waking state. CONCLUSIONS: The effect of pain modulation is limited to high hypnotizable subjects rather than low hypnotizable ones. Higher frontal-temporal N2 and smaller posterior parietal P3 may indicate active inhibitory processes during cognitive strategies in hypnotic analgesia. These inhibitory processes also regulate the autonomic activities in pain perception.

Adult↗
PubMed2000

Nurses' perceptions of pain assessment and treatment in the cognitively impaired elderly. It's not a guessing game.

The purpose of the study was to describe nurses' perceptions regarding the assessment and treatment of pain in patients with late-stage dementia. Thirty nurses from six long-term care facilities were interviewed using a semistructured format for this qualitative study. Initial results were presented to a second group for validation and refinement of findings. The most commonly cited behaviors used to indicate discomfort were facial grimacing, restless body movement, change in behavior, moaning, and tense muscles. Psychotropic drugs were perceived to be commonly misused because behavior changes were seen as a psychiatric problem rather than a representation of the patient's unmet need. Nurses had positive feelings about using both narcotics and nonnarcotic analgesics with this population but believed both types of analgesics were underused. The most common concerns regarding the administration of narcotic analgesics to this population were falls, sedation, and constipation.

Aged↗
PubMed1975

The decompensated back.

There is no single circumstance or combination of circumstances which precipitate all clinical instances of back discomfort. This simple statement should be so obvious that one must question the finality and accuracy of the diagnostic effort in those reports which relate to large series of patients treated by one method. There is no thought of impugning the basic honesty of the reporting physician in this statement, but rather of raising the fair question of whether the "slipped disc" (or whatever the etiological diagnosis) is all that happened to produce the symptoms, and whether its removal (or whatever) is all that occurred in accomplishing clinical cure improvement. If there is doubt that the answer to both questions is in the affirmative, then serious consideration must be given to those other factors, if the medical profession is ever to be a science instead of a trade. The back structures are different from comparable structures elsewhere in the body, principally in their neurological organization and controlmthere is the specific, discrete, segmental arrangement of both sensory and motor functions of muscular and nonmuscular structures via the posterior primary rami of the spinal nerves. Coupled with this is a different mechanism of segmental innervation of the vascular and nonmuscular structures which line the vertebral canal, via the sinu-vertebral nerves. Both are modulated by higher level influences. The sinu-vertebral nerves, through the sympathetic chain, may provide an additional avenue of response which may avoid or alter the influence of higher levels. The Melzack-Wall hypothesis would seem to provide an acceptable explanation for the need to modulate nociceptive afferent stimuli before they evoke pain perception and response. Since this modulation mechanism decompensates under numerous conditions, pain perception and responses do occur. Among those responses are the alterations in normal function of the low back structures, perhaps the disastrously effective one of which is decompensation of the muscular strength necessary to accomplish the demands of daily use. This problem is not so simply solved by a handout sheet of exercises. The primary consideration is to modify or relieve pain by a careful evaluation of its source and the employment in combination of those therapeutic efforts which a logical treatment plan indicates. If these be accomplished, the final and most important consideration, then, is the improvement of neuromuscular function to the level compatible with normal activities by a carefully guided activity program. There is no method for instant reversal of the status of the decompensated heart--nor the decompensated back.

Adult↗
PubMed1997

Tonic pain: a SPET study in normal subjects and cluster headache patients.

Whether the pathogenesis of cluster headache (CH) is peripheral or central is still matter of debate. An involvement of central structures related to pain perception and modulation, which also causes an alteration of the physiological pattern of pain perception in CH, has been hypothesized. We investigated the pattern of brain response to pain in normal subjects and CH patients by evaluating the cerebral blood flow (CBF) changes using an experimental model of tonic aching pain stimulation, the cold water pressor test (CWPT). CBF was assessed quantitatively by the Xe-133 inhalation method and single photon emission tomography (SPET), at rest and during CWPT, as previously described (Di Piero et al., 1994). CWPT was performed in 12 volunteers and in seven patients with CH. All the CH patients had a left-sided headache and were studied in a headache-free phase out of the cluster period. During CWPT, volunteers showed a significant CBF increase in the contralateral primary sensorimotor (P < 0.001), frontal (P < 0.01) and temporal (P < 0.002) regions and thalamus (P < 0.01) and in the ipsilateral temporal (P < 0.005) and anterior cingulate (P < 0.01) regions. During left-hand stimulation (ipsilateral to the headache side) by CWPT in CH patients, CBF changes were significantly lower than those observed in volunteers in the contralateral primary sensorimotor region (P < 0.0005) and thalamus region (P < 0.01). There were no significant differences in the brain response observed during the stimulation of the hand contralateral to the headache side. In conclusion, in a headache-free phase out of the cluster period, the pattern of cerebral activation during tonic pain stimulation of the hand ipsilateral to the headache side is critically modified in CH patients in areas which are probably involved in the detection of the stimulus intensity. This modification may reflect a marker of a biological modification of the pain conveyance system. The fact that it is also present out of the active period of the disease, suggests a possible involvement of central tonic pain mechanisms in the pathogenesis of CH.

Adult↗
PubMed2000

Treatment of dentinal hypersensitivity using a dentine bonding system.

AIMS AND OBJECTIVES: Many agents have been used in treatment of dentinal hypersensitivity in the past, but dentine bonding systems have recently been suggested as being effective. This study examined the effectiveness of a dentine bonding system in the treatment of dentinal hypersensitivity in dental practice conditions. METHODS: Dentists in two dental practices agreed to carry out the project. One practice was in the UK, the other in India. A total of 34 patients who were diagnosed to have dentinal hypersensitivity were treated using the dentine bonding system. Patients were requested to record their perception of their pain on a 100mm linear scale, pre-treatment, one day and one week post-treatment. RESULTS: All patients experienced relief of pain, both 1 day and 1 week after treatment. Profile plots of the patients' perceived pain scores for the two practices separately indicated that there was a general trend across both practices for these to fall quite sharply one day after treatment and then generally level out one week post-treatment. There was evidence indicating a possible difference in pain perception in the two communities from which the patients were drawn. CONCLUSION: The dentine bonding system evaluated was successful in reducing the pain of dentinal hypersensitivity, at least in the short term.

Analysis of Variance↗
PubMed2001

The association of hormone replacement therapy with experimental pain responses in postmenopausal women.

Considerable experimental research suggests that ovarian hormones can influence pain perception, and recent epidemiologic and clinical research suggests that exogenous hormone use may influence the prevalence and severity of clinical pain among women. However, to date no studies have examined the influence of hormone replacement therapy (HRT) on experimental pain responses and recent pain complaints among postmenopausal women. In this study, self-reported recent pain and general health were obtained, and thermal pain responses were assessed in three groups of healthy older adults: (1) women on HRT, (2) women not on HRT (No-HRT), and (3) men. Results indicated no group differences in recent pain complaints or self-reported health, but differences emerged for measures of thermal pain perception. Specifically, HRT women showed lower pain thresholds and tolerances than No-HRT women and men, and the latter two groups did not differ from each other. The potential explanations and limitations of the observed findings are discussed.

Aged↗
PubMed2003

Left-hemisphere dominance in early nociceptive processing in the human parasylvian cortex.

Pain perception comprises sensory and emotional dimensions. While the emotional experience is thought to be represented in the right hemisphere, we here report a left-hemisphere dominance for the early sensory component of pain perception using brain electrical source analysis of laser-evoked potentials. Ten right-handed subjects underwent several series of laser radiant heat stimuli to pairs of parallel lines on the dorsum of the left or right hand. Stimulus location and intensity were randomised independently. The sensory-discriminative aspects of pain were emphasised by asking the subjects to perform either a spatial or an intensity discrimination task and were contrasted with active distraction by mental arithmetics. Pain ratings obtained after each of the laser stimulus series revealed an analgesic effect of distraction (27%, P < 0.001). Four equivalent dipole sources were active in the latency range of 100-200 ms (bilateral operculoinsular cortex, midcingulate gyrus, postcentral gyrus). The sources in the operculoinsular cortex exhibited (a) the shortest peak latency (155 +/- 6 ms), (b) the most pronounced enhancement during spatial and intensity discrimination tasks compared to active distraction (43%, P < 0.001), and (c) a significantly stronger source activity in the left hemisphere independent of stimulation side (23%, P < 0.05). The distribution of these sources extended into the dorsal insula. The postcentral source had the longest peak latency (180 +/- 7 ms); its source strength was task-dependent (25%, P = 0.051) but exhibited no hemisphere dominance. The midcingulate source had an intermediate peak latency (169 +/- 7 ms). Its source strength was modulated by tasks, but this modulation was significant only in the latency range >200 ms (46%, P < 0.001). These findings suggest a dominant role of the left frontal operculum and adjacent dorsal insula in the early sensory-discriminative dimensions of pain processing. This region has been proposed to be the cortical projection target of nociceptive pathways from the spinal cord to the ventroposteroinferior and ventromedial (its posterior part: VMpo) thalamic nuclei.

Adult↗
PubMed2005

Comparison of different local anesthesia techniques during TRUS-guided biopsies: a prospective pilot study.

OBJECTIVES: To introduce two forms of anesthesia and compare them with standard local anesthesia techniques. METHODS: A total of 114 consecutive patients underwent prostate needle biopsy. The patients were sequentially randomized to receive different kinds of anesthesia: 2% rectal lidocaine gel, 40% dimethyl sulfoxide (DMSO) with lidocaine, perianal injection of 1% lidocaine, or periprostatic nerve block. Pain perception was separately assessed for probe insertion and biopsies using a visual pain analog score. One-way analysis of variance was used to compare the data scale among the four groups. A linear regression model was used to define the independent variables that predicted the level of pain. RESULTS: The groups were similar in terms of age, prostate-specific antigen levels, digital rectal examination findings, prostate volume, pain tolerance, biopsy time, and number of cores taken. The lowest pain scores for probe insertion were for the perianal injection and DMSO/lidocaine groups (0.89 and 1.38, respectively). The difference between these scores and those for the other two groups was statistically significant (P <0.001). Pain perception during biopsy did not differ significantly among the DMSO/lidocaine, perianal, or periprostatic groups and was greatest in the lidocaine gel group (4.147; P <0.001). We did not observe any statistically significant correlation between the pain level during probe insertion and biopsy and pain tolerance (P = 0.514 and P = 0.788, respectively). The anesthesia type was the strongest single predictor of the pain level during biopsy (P <0.001). CONCLUSIONS: The use of 40% DMSO with lidocaine instilled into the rectal vault for 10 minutes avoids any need for injection and is capable of decreasing the discomfort or pain experienced during probe insertion and prostate biopsy comparable to the perianal and periprostatic protocols.

Adenocarcinoma↗
PubMed2004

Synthesis of urea-based inhibitors as active site probes of glutamate carboxypeptidase II: efficacy as analgesic agents.

The neuropeptidase glutamate carboxypeptidase II (GCPII) hydrolyzes N-acetyl-L-aspartyl-L-glutamate (NAAG) to liberate N-acetylaspartate and glutamate. GCPII was originally cloned as PSMA, an M(r) 100,000 type II transmembrane glycoprotein highly expressed in prostate tissues. PSMA/GCPII is located on the short arm of chromosome 11 and functions as both a folate hydrolase and a neuropeptidase. Inhibition of brain GCPII may have therapeutic potential in the treatment of certain disease states arising from pathologically overactivated glutamate receptors. Recently, we reported that certain urea-based structures act as potent inhibitors of GCPII (J. Med. Chem. 2001, 44, 298). However, many of the potent GCPII inhibitors prepared to date are highly polar compounds and therefore do not readily penetrate the blood-brain barrier. Herein, we elaborate on the synthesis of a series of potent, urea-based GCPII inhibitors from the lead compound 3 and provide assay data for these ligands against human GCPII. Moreover, we provide data revealing the ability of one of these compounds, namely, 8d, to reduce the perception of inflammatory pain. Within the present series, the gamma-tetrazole bearing glutamate isostere 7d is the most potent inhibitor with a K(i) of 0.9 nM. The biological evaluation of these compounds revealed that the active site of GCPII likely comprises two regions, namely, the pharmacophore subpocket and the nonpharmacophore subpocket. The pharmacophore subpocket is very sensitive to structural changes, and thus, it appears important to keep one of the glutamic acid moieties intact to maintain the potency of the GCPII inhibitors. The site encompassing the nonpharmacophore subpocket that binds to glutamate's alpha-carboxyl group is sensitive to structural change, as shown by compounds 6b and 7b. However, the other region of the nonpharmacophore subpocket can accommodate both hydrophobic and hydrophilic groups. Thus, an aromatic ring can be introduced to the inhibitor, as in 8b and 8d, thereby increasing its hydrophobicity and thus potentially its ability to cross the blood-brain barrier. Intrathecally administered 8d significantly reduced pain perception in the formalin model of rat sensory nerve injury. A maximal dose of morphine (10 mg) applied in the same experimental paradigm provided no significant increase in analgesia in comparison to 8d during phase 1 of this pain study and modestly greater analgesia than 8d in phase 2. These urea-based inhibitors of GCPII thus offer a novel approach to pain management.

Analgesics↗