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PubMed2006

Functional neuroanatomy of the hypnotic state.

The neural mechanisms underlying hypnosis and especially the modulation of pain perception by hypnosis remain obscure. Using PET we first described the distribution of regional cerebral blood flow during the hypnotic state. Hypnosis relied on revivification of pleasant autobiographical memories and was compared to imaging autobiographical material in "normal alertness". The hypnotic state was related to the activation of a widespread set of cortical areas involving occipital, parietal, precentral, premotor, and ventrolateral prefrontal and anterior cingulate cortices. This pattern of activation shares some similarities with mental imagery, from which it mainly differs by the relative deactivation of precuneus. Second, we looked at the anti-nociceptive effects of hypnosis. Compared to the resting state, hypnosis reduced pain perception by approximately 50%. The hypnosis-induced reduction of affective and sensory responses to noxious thermal stimulation were modulated by the activity in the midcingulate cortex (area 24a'). Finally, we assessed changes in cerebral functional connectivity related to hypnosis. Compared to normal alertness (i.e., rest and mental imagery), the hypnotic state, significantly enhanced the functional modulation between midcingulate cortex and a large neural network involved in sensory, affective, cognitive and behavioral aspects of nociception. These findings show that not only pharmacological but also psychological strategies for pain control can modulate the cerebral network involved in noxious perception.

Brain↗

PubMed2006

[Pain processing in patients with borderline personality disorder, fibromyalgia, and post-traumatic stress disorder].

The authors review relevant experimental studies on pain perception and processing in psychiatric disorders with traumatic stress as an etiological factor. In borderline personality disorder, post-traumatic stress disorder, and fibromyalgia neurophysiological and neuropsychological patterns of pain processing appear to be different. Experimental studies in borderline patients show a desensitization of pain thresholds whereas patients with fibromyalgia show an opposite pattern, which could be explained by a central augmentation of pain processing. Furthermore, the authors outline methods to assess pain perception (peripheral and central) and describe the neurobiological mechanisms of pain processing, particularly the distinction between the sensory-discriminative lateral system and the affective-motivational medial system. Finally, suggestions for further research and implications for therapy are proposed.

Central Nervous System↗

PubMed2004

Liquid growth hormone: preservatives and buffers.

Growth hormone (GH) treatment is a successful medical therapy for children and adults with GH deficiency as well as for growth retardation due to chronic renal disease, Turner syndrome and in children born small for gestational age. For all of these conditions, treatment is long term and patients receive daily subcutaneous injections of GH for many years. Patient compliance is therefore of critical importance to ensure treatment benefit. One of the major factors influencing compliance is injection pain. Besides the injection device used, pain perception and local tissue reaction following injection are dependent on the preservative used in the formulation and the concentration of GH. Injection pain may also be related to the buffer substance and injection volume. A liquid formulation of GH, Norditropi SimpleXx, has been developed that dispenses with the need for reconstitution before administration. The formulation uses phenol (3 mg/ml) as a preservative (to protect product from microbial degradation or contamination) and histidine as a buffer. Alternative preservatives used in other GH formulations include m-cresol (9 mg/ml) and benzyl alcohol (3-9 mg/ml). Buffering agents include citrate and phosphate. Phenol has been successfully used as a preservative in drug formulations for more than 50 years and is considered a safe and effective agent which complies with strict international requirements for preservatives in drug formulations. In toxicological studies, no or only mild local reactions have been observed following subcutaneous administration of phenol (7.5 mg/ml), m-cresol (3-4 mg/ml) and benzyl alcohol (9 mg/ml). No general toxicity reactions were observed after subcutaneous administration of these agents. Clinical evaluation of the preservatives and buffers used in Norditropin SimpleXx showed that pain perception was similar between formulations containing phenol and benzyl alcohol, whereas m-cresol was associated with more painful injections than benzyl alcohol. Furthermore, patients reported more pain following injection of a citrate-buffered solution than after a histidine-buffered solution. More pain was also reported following large volume injections and following injections with solutions containing high protein concentrations. In summary, optimization of the preservative and buffer content of a liquid GH formulation may reduce injection pain and lead to improved patient compliance.

Buffers↗

PubMed1999

Lack of local anaesthetic efficacy of fentanyl in the abaxial sesamoid block model.

Fentanyl and other opioid drugs have their effect in the central nervous system; however, activity at peripheral sites has also been demonstrated. Pain-suppression activity at peripheral sites raises the possibility of skilled individuals producing local anaesthetic effects with small doses of opioid drugs that would be difficult to detect forensically and could be used to affect the outcome of a race. Therefore, the local pain-suppression effect (peripheral nerve inhibition) of fentanyl was tested using an abaxial sesamoid block/hoof withdrawal model. With this model, fentanyl did not produce significant anaesthesia when tested in eight Thoroughbred horses. This suggests that fentanyl at this or lower doses is unlikely to reduce pain perception when applied directly to sensory neurons. However, the effect of fentanyl and other opioids on joint pain perception of horses, especially inflamed joints, is unknown.

Analgesics, Opioid↗

PubMed2006

Age-related impact of neuropathic pain on animal behaviour.

The number of old and very old persons is increasing and there is evidence that aging coincides with chronic painful conditions. Pain induces behavioural disorders that have been so far poorly identified in old and even less in very old animals. The aim of this study was to: (1) compare the evolution of pain in senescent animals (37-39 months) to old (20-22 months) and young (4-6 months) Lou/cjall rats after a chronic constriction of the sciatic nerve; (2) evaluate pain during four weeks after surgery with an experimental and an observational approach to determine how the response to noxious stimuli correlates with recorded spontaneous behaviour. Results showed that senescent animals are less sensitive to neuropathic pain than old or young rats while senescent/old rats are more sensitive to acute pain. The correlation between observational and experimental pain scores stresses the reliability of non-invasive measures for pain evaluation in senescent populations. The dichotomy between neuropathic and acute pain perceptions with age needs to be further investigated and would help to better understand the reasons of this uneven pain perception and expression with age.

Acute Disease↗

PubMed2001

Analgesia and cyclo-oxygenase inhibitors.

Non-steroidal anti-inflammatory drugs are among the most commonly used medications and they are a mainstay in the treatment of inflammatory diseases. Non-steroidal anti-inflammatory drugs are widely used to reduce pain associated with acute or chronic inflammation. Recently, a new class of inhibitors of the inducible enzyme cyclo-oxygenase-2 have become available. These inhibitors selectively target the inducible enzyme and have been shown to spare the gastrointestinal tract. While a role of cyclo-oxygenase-2 in the development of chronic inflammation has been well established, its role in pain perception is still unclear. Recent experimental data led to the hypothesis that cyclo-oxygenase-1 plays an important role in pain perception. This short review addresses some recent preclinical data as well as some clinical evidence showing that cyclo-oxygenase-1 is an important component of inflammatory pain.

Analgesics↗

PubMed1999

Sensation recovery on innervated radial forearm flap for hemiglossectomy reconstruction by using different recipient nerves.

The objectives of this study were (1) to determine the extent of sensory recovery on hemitongues reconstructed with innervated radial forearm flaps and (2) to assess the influence of various clinical and surgical factors over the return of sensation, including the use of different recipient nerves for neurorrhaphy. Twenty-eight patients with tongue cancer who underwent hemiglossectomy and primary reconstruction with innervated radial forearm flaps over a 3-year period were studied. Mean postoperative follow-up was 18.2 months (range 6 to 32 months). Sensory recovery was assessed in a blind manner by two examiners that used (1) static two-point discrimination, (2) light touch sensation, (3) pain perception, and (4) hot and cold temperature perception. Different surfaces were assessed with each method on the reconstructed hemitongue and on the intact contralateral hemitongue (used as control). The following factors and their relationship with flap sensory recovery were analyzed: age, smoking history, size of the reconstructed defect, administration of postoperative radiation therapy, recipient nerve, and neurorrhaphy technique. Comparative statistical analysis (p < 0.05) between both hemitongues was performed using paired t test followed by Bonferroni correction for static two-point discrimination and light touch sensation. Fisher exact test analysis was used for pinprick and hot and cold temperature perception. The control side was ignored in analyzing the effects of the risk factors. The tip, dorsal aspect, ventral surface, and floor of mouth on the reconstructed hemitongue had comparable static two-point discrimination when compared with the intact hemitongue. Light touch sensation was also similar in the tip and dorsal aspect of both hemitongues; however, a statistically significant difference (p < 0.05) was observed on the ventral surface and floor of mouth of the reconstructed hemitongues. Likewise, pain perception was significantly decreased in the floor of the mouth, compared with other surfaces. No clearly dependent association was established between return of flap sensation and age, tobacco use, and size of the reconstructed defect. Light touch sensation, pain, and temperature perception were significantly decreased when the patients had received postoperative radiation therapy. In addition, all four sensory tests were significantly diminished (p < 0.05) when the recipient nerve used for neurorrhaphy was a nerve other than the lingual or the inferior alveolar nerve, and also when an end-to-side nerve repair was used. Sensation recovery of the innervated radial forearm flap after hemitongue reconstruction approaches normal compared with the contralateral intact hemitongue. Lower return of sensation may be anticipated in patients who receive postoperative radiotherapy. Good recovery of sensation is predictable when either the lingual or inferior alveolar nerve is used for neurorrhaphy, in contrast to using other recipient nerves.

Adult↗

PubMed2004

Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome.

BACKGROUND & AIMS: The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell infiltration may perturb nerve function leading to symptom perception. We assessed colonic mast cell infiltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients. METHODS: IBS patients were diagnosed according to Rome II criteria and abdominal pain quantified according to a validated questionnaire. Colonic mucosal mast cells were identified immunohistochemically and quantified with a computer-assisted counting method. Mast cell tryptase and histamine release were analyzed immunoenzymatically. Intestinal nerve to mast cell distance was assessed with electron microscopy. RESULTS: Thirty-four out of 44 IBS patients (77%) showed an increased area of mucosa occupied by mast cells as compared with controls (9.2% +/- 2.5% vs. 3.3 +/- 0.8%, respectively; P < 0.001). There was a 150% increase in the number of degranulating mast cells (4.76 +/- 3.18/field vs. 2.42 +/- 2.26/field, respectively; P = 0.026). Mucosal content of tryptase was increased in IBS and mast cells spontaneously released more tryptase (3.22 +/- 3.48 pmol/min/mg vs. 0.87 +/- 0.65 pmol/min/mg, respectively; P = 0.015) and histamine (339.7 +/- 59.0 ng/g vs. 169.3 +/- 130.6 ng/g, respectively; P = 0.015). Mast cells located within 5 microm of nerve fibers were 7.14 +/- 3.87/field vs. 2.27 +/- 1.63/field in IBS vs. controls (P < 0.001). Only mast cells in close proximity to nerves were significantly correlated with severity and frequency of abdominal pain/discomfort (P < 0.001 and P = 0.003, respectively). CONCLUSIONS: Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.

Abdominal Pain↗

PubMed2005

Individual differences in pain responses.

The experience of pain is characterized by tremendous inter-individual variability. Indeed, an identical noxious stimulus can produce vastly different pain responses across individuals. Historically, scientists have regarded this variability as a nuisance; however, substantial data suggest that these individual differences may provide valuable information that can be used to enhance clinical management of pain. This paper discusses several factors that contribute to individual differences in pain perception, including demographic (ie, sex, age, and ethnicity), genetic, and psychosocial variables. These factors are discussed in the context of the biopsychosocial model of pain, which posits that pain perception is influenced by interactions among biologic, psychosocial, and sociocultural factors. Finally, the clinical and scientific implications of individual differences in pain are discussed.

Age Factors↗

PubMed1981

Effects of lithium salts on pain experience in depressed patients.

15 depressed female patients were studied for sensitivity to pain stimuli before and after 1 month of treatment with lithium salts. By electric stimulation techniques, an aspecific sensitivity threshold, a pain sensitivity threshold and a pain tolerance threshold were measured and their relationship were evaluated. In this investigation, we evaluated the influence of the improvement of the clinical picture and of the blood levels of the drug on pain perception. Our data seem to suggest an analgesic action of lithium, which, however, appears to be partially masked by the effects on pain perception induced by the evolution of the depressive picture.

Depressive Disorder↗

PubMedDate not supplied

Ethnographic assessment of pain coping perceptions.

A sample consisting of 54 patients and 31 dentists of Chinese, Anglo-American, and Scandinavian ethnic origin were interviewed about their ways of coping with pain. Instruments designed to assess pain coping were constructed from the descriptions elicited by the interviews. The interview data thus served as the basis for cross-cultural quantitative indices. Content analysis of the interviews revealed significant differences between patients and dentists and an East-West ethnic difference between patient groups. Anglo-American patients and all dentists preferred internally applied medicines (pills, injections etc.). Chinese patients preferred external agents (salves, oils, massage, etc.) significantly more than Chinese dentists or Western subjects. Swedish and Chinese patients preferred not to use local anesthesia for dental treatment. These results were corroborated by nonparametric and multidimensional scaling analyses of the cross-cultural quantitative data. Professional socialization had a stronger influence on pain remedy description than did ethnicity, while patient descriptions of remedies appeared to be more ethnospecific, especially showing East-West differences. These anthropologic methods appeared to be valid and reliable in revealing cognitive processes involved in the pain coping preferences of these subjects.

Adaptation, Psychological↗

PubMed1989

Nurses' perceptions of pain in the neonatal intensive care unit.

Pain in neonates has only recently become the focus of clinical and research attention. Measurement of pain in this population presents special problems. Neonatal nurses were selected as observers and recorders of neonatal pain behavior, as they are in constant contact with neonates undergoing aversive procedures, and thus have special expertise in this area. This study used a questionnaire to examine the perceptions of neonatal nurses as to the indicators and causes of different intensities of pain. Nurses used similar classes of behavior to indicate pain, but varied somewhat in the specific behavioral indicators for different levels of pain. A very wide range of sources of pain was identified.

Child Behavior↗

PubMed2003

Morphine withdrawal is modified in pituitary adenylate cyclase-activating polypeptide type I-receptor-deficient mice.

The pituitary adenylate cyclase-activating polypeptide type I-receptor (PAC1) is a G-protein-coupled receptor that is widely expressed in neurons of the central and peripheral nervous system. The strong expression of PAC1 in the second sensory neuron as well as in brainstem regions such as the locus coeruleus prompted us to elucidate the potential in vivo role of PAC1-mediated signalling in pain perception and opioid addiction using a PAC1-deficient mouse line. We observed a selective involvement of PAC1 in the mediation of visceral pain. While there was no impairment in acute somatic pain perception, PAC1-mutants exhibited a dramatically decreased response in the abdominal writhing test. These data in concert with data from the literature implicate PAC1 in the mediation of visceral and chronic pain. In addition, we observed that PAC1 did not influence the motivational aspects of opioid addictive properties, since morphine-induced rewarding effects and sensitization to locomotor responses were completely maintained in PAC1-deficient mice. However, there was a dramatic increase in physical withdrawal signs after naloxone-precipitated morphine withdrawal in PAC1 mutants. At the cellular level, electrophysiological examinations in locus coeruleus neurons from morphine-dependent wild-type and PAC1-deficient mice did not reveal any differences in firing rates. These data therefore suggested that most likely disruption of PAC1-mediated signalling in afferents towards the locus coeruleus but not within the intrinsic locus coeruleus system led to the enhancement of somatic withdrawal signs.

Analgesics, Opioid↗

PubMed2003

Women experience more pain and require more morphine than men to achieve a similar degree of analgesia.

UNLABELLED: Sex differences in pain perception and in response to opioids have been described, but the findings are inconsistent. We sought to determine the effect of sex on pain perception, morphine consumption, and morphine analgesia after surgery. We designed a prospective cohort study and included 423 women and 277 men who emerged from general anesthesia after surgical procedures and who reported pain intensity of >or=5 on the 0-10 numeric rating scale (NRS). We administered 2.5 mg of morphine IV every 10 min until the pain intensity was <or=4 of 10. Every 10 min, patients rated their pain on the NRS and indicated the degree of pain relief on a 5-point Likert scale. After adjustment for type of operation and age, we found that women had more intense pain and had larger morphine consumption than men. The difference in NRS pain intensity was 0.4 U (95% confidence interval, 0.1-0.6 U). Women required 0.03 mg/kg more morphine than men (95% confidence interval, 0.02-0.04 mg/kg). We conclude that women have more intense pain and require 30% more morphine to achieve a similar degree of analgesia compared with men. Clinicians should anticipate the differences in opioid requirement to avoid undertreatment of pain in women. IMPLICATIONS: The effect of sex on opioid response is not clear. To determine the effect of sex on morphine consumption and morphine analgesia, we designed a cohort study. We found that women had more intense pain and required 30% more morphine to achieve a similar degree of analgesia compared with men.

Abdomen↗

PubMed2001

Does exogenous melatonin influence the free radicals metabolism and pain sensation in rat?

Melatonin has been shown to play a role in antioxidative defence. We therefore studied its effect on oxidative damage to the rat cerebral cortex evoked by painful stimulation and immobilization-induced stress. Moreover, the effect of melatonin on chronic pain perception was examined. Rats were injected with either a high dose of melatonin (100 mg/kg i.p.) or a vehicle for five days and were subjected to painful stimulation or immobilization stress 30 min after the treatment. To determine the degree of oxidative stress, the levels of free radicals, thiobarbituric acid reactive substances (TBARS) as indicators of lipid peroxidation and glutathione peroxidase (GSHPx) were estimated in somatosensory cortex. Pain perception was measured by the tail-flick and plantar test. Melatonin reduced the level of TBARS previously increased by painful stimulation. Melatonin also exhibited a slight analgesic effect in those animals exposed to painful stimulation but its role in free radical scavenging did not contribute to this effect.

Animals↗

PubMed1992

An application of the fear avoidance model to three chronic pain problems.

The Fear Avoidance Model of Exaggerated Pain Perception was developed in an attempt to explain how, and why, some individuals develop a more substantial psychological overlay to their low back pain problem than do others. The present paper describes a study in which three chronic pain groups, consisting of Post-Herpetic neuralgia patients, Reflex Sympathetic Dystrophy patients and chronic low back pain patients were compared with three pain-free comparison groups using the Fear Avoidance Model of Exaggerated Pain Perception. The results show statistically significant differences between the chronic groups and the recovered comparison groups. These results demonstrate the usefulness of the Fear Avoidance Model as an explanation of psychological overlay in chronic pain conditions regardless of pathology.

Adaptation, Psychological↗

PubMed2006

Embolotherapy for pelvic congestion syndrome: long-term results.

PURPOSE: To evaluate the long-term clinical outcome of transcatheter embolotherapy in women with chronic pelvic pain caused by ovarian and pelvic varices. MATERIALS AND METHODS: The study population included consecutive patients referred to a tertiary-care interventional radiology service from 1998 to 2003 because of a high degree of clinical suspicion of pelvic and ovarian varices. Visual analog scales and questionnaires during clinic visits were used to measure pain perception levels. Basal female hormonal levels were obtained and compared. RESULTS: Of 131 patients referred (mean age, 34.0 years+/-12.5), percutaneous transfemoral venography confirmed the presence of ovarian varices in 127 (97.0%), all of whom were treated with embolotherapy. Internal iliac embolotherapy was performed in 108 of 127 patients (85.0%). Ninety-seven patients completed long-term clinical follow-up (mean 45 months+/-18). The mean pelvic pain level had improved significantly from 7.6+/-1.8 before embolotherapy to 2.9+/-2.8 after embolotherapy (P<.0001). Significant improvement in each category of specific symptoms was also noted (P<.0001). Overall, 83% of the patients exhibited clinical improvement at long-term follow-up, 13% had no significant change, and 4% exhibited worsened condition. No significant change was noted in hormone levels after embolotherapy. Two successful pregnancies were noted after ovarian and pelvic vein embolotherapy. CONCLUSION: Direct venographic evaluation with embolotherapy can achieve significant improvement in pain perception levels in patients with chronic pelvic pain caused by pelvic venous congestion.

Adult↗

PubMed1999

Visceral algesia in irritable bowel syndrome, fibromyalgia, and sphincter of oddi dysfunction, type III.

Visceral hyperalgesia has been demonstrated in patients with irritable bowel syndrome who are seen in tertiary care centers. It has been hypothesized that visceral hyperalgesia may be related to psychological distress associated with health care seeking behavior in these patients. Patients with fibromyalgia and sphincter of Oddi dysfunction, type III, share many demographic and psychosocial characteristics with patients with irritable bowel syndrome and provide an opportunity to test the hypothesis that rectal hyperalgesia is unique to IBS. Fifteen patients with IBS, 10 patients with fibromyalgia, 10 with sphincter of Oddi dysfunction, type III, and 12 controls underwent evaluation of rectal pain perception in response to phasic distensions and psychological testing with a self-report instrument. Patients with irritable bowel syndrome demonstrated significantly lower rectal pain thresholds and increased levels of psychologic distress compared to controls. Although sphincter of Oddi dysfunction patients also exhibited increased psychologic distress, rectal pain perception was similar to controls. Patients with fibromyalgia exhibited rectal algesia that was not significantly different from either controls or IBS. In conclusion, rectal hyperalgesia is not a function of chronic functional pain, health care seeking behavior, or psychological distress. However, it may not be specific for IBS.

Adult↗