Trigeminal neuropathic pain: pathophysiological mechanisms examined by quantitative assessment of abnormal pain and sensory perception

OBJECTIVE: This study was undertaken to examine the pathophysiological characteristics of trigeminal neuropathic pain. METHODS: The study included 23 consecutive patients with trigeminal neuropathic pain (15 patients with pain after nerve injury and 8 patients with pain of spontaneous origin). For each patient, quantitative examination of sensory and pain perception was performed in the painful facial skin area, and results were compared with the findings for the contralateral nonpainful facial skin area. RESULTS: In the painful facial skin area of patients with neuropathic pain after nerve injury, we demonstrated increased temperature and tactile thresholds, as well as abnormal temporal summation of pain (i.e., repetitive nonpainful skin stimulation produced an abnormal progressive increase of pain intensity, with abnormal radiation of pain and aftersensation). In the painful skin area of patients with pain of spontaneous origin, temperature and tactile thresholds were not increased, but heat pain and cold pain thresholds were significantly reduced, indicating heat and cold hyperalgesia. The characteristics of temporal summation of pain were not significantly altered in the painful facial skin area in this group of patients. CONCLUSION: This clinical study provides evidence that the pathophysiological mechanisms of trigeminal neuropathic pain after nerve injury involve impaired function of both small unmyelinated fibers and large myelinated fibers. An explanation for the finding of abnormal temporal summation of pain may involve hyperexcitability of central wide-dynamic range neurons. The results suggest that other mechanisms are involved in trigeminal neuropathic pain of spontaneous origin. Reduced heat and cold pain thresholds indicate heat and cold hyperalgesia, which possibly may be explained by sensitization of peripheral C nociceptors.     

Relationship between pain sensitivity and resting arterial blood pressure in patients with painful temporomandibular disorders

OBJECTIVE: Patients experiencing temporomandibular disorders (TMD) show greater sensitivity to painful stimuli than age- and gender-matched control subjects. This enhanced pain sensitivity may result, at least in part, from an alteration in pain regulatory systems that are influenced by resting arterial blood pressure. In this study, we examined the relationship between resting systolic blood pressure and pain perception in 64 female TMD and 23 age-matched pain-free female subjects. METHOD: Resting arterial blood pressure and measures of thermal and ischemic pain threshold and tolerance were determined for each participant. Subjective ratings of thermal pain evoked by suprathreshold noxious thermal stimuli (45-49 degrees C) using a magnitude matching procedure were also obtained for both groups. RESULTS: TMD patients had lower thermal and ischemic pain thresholds and tolerances than pain-free subjects (ps < .05). Both groups provided equivalent intensity ratings to suprathreshold noxious thermal stimuli. A median split of each group based on resting systolic blood pressure revealed an influence of blood pressure on both thermal and ischemic pain perception for the Pain-Free group. The Pain-Free high resting blood pressure subgroup had higher thermal pain tolerances, higher ischemic pain thresholds, and provided lower magnitude estimates of the intensity of graded heat pulses compared with the Pain-Free low blood pressure subgroup. A trend toward a significant effect of blood pressure level on ischemic pain tolerance was also observed for the Pain-Free group. In contrast to the Pain-Free group, blood pressure level did not influence ischemic or thermal pain perception for TMD patients. Similar to the lack of effect of resting blood pressure on experimental pain perception in TMD patients, resting blood pressure was not related to measures of clinical orofacial pain in TMD patients. CONCLUSIONS: These findings confirm our previous findings that TMD patients are more sensitive to noxious stimuli and suggest that painful TMD may result, at least in part, from an impairment in central pain regulatory systems that are influenced by resting arterial blood pressure.     

The effect of peripheral glycerol on trigeminal neuropathic pain examined by quantitative assessment of abnormal pain and sensory perception

In nine patients with trigeminal neuropathic pain after nerve injury, we examined prospectively the effect of peripheral glycerol neurolysis on abnormal pain and sensory perception. In the painful facial skin area of these patients, we found increased temperature and tactile thresholds and the presence of abnormal temporal summation of pain. In seven patients, neuropathic pain was peripheral and disappeared after application of local anaesthesia at or proximal to the site of nerve injury. Neuropathic pain was central in two patients, and unresponsive to local anaesthesia applied proximal to the site of nerve injury. Six weeks after injection of glycerol proximal to the site of nerve injury, no or marginal pain relief was found in 8 patients with peripheral or central trigeminal neuropathic pain. On the other hand, in one of the patients with peripheral trigeminal neuropathic pain, glycerol was given at the site of nerve injury, and produced total pain relief for the whole observation period of 7 months. In this patient, pain relief was associated with normalisation of abnormal temporal summation of pain, which was not observed in the 8 patients with no or marginal pain relief. No further changes in temperature or tactile thresholds were found in any of the 9 patients after a single injection of absolute glycerol. Total pain relief in one of the patients probably is related to the ability of glycerol to inhibit ongoing ectopic impulse generation at the site of nerve injury. We suggest that glycerol-induced reduction of primary afferent hyperactivity may secondarily result in down-regulation of central neuronal hyperexcitability. The efficacy of application of glycerol at the site of nerve injury in patients with peripheral trigeminal neuropathic pain may warrant further investigation. However, this prospective study does not provide evidence that application of glycerol proximal to the site of nerve injury has a place in the treatment of trigeminal neuropathic pain.     

Functional dyspepsia and irritable bowel syndrome: is there a common pathophysiological basis?

OBJECTIVES: Alterations of mechanosensitive thresholds occur in a subset of patients with functional dyspepsia and irritable bowel syndrome (IBS). However, symptoms associated with these two conditions frequently overlap. It is not known how often subjects with and without symptom overlap have abnormal intestinal sensory thresholds. Our objective was to assess the pattern of symptoms and small intestinal sensory thresholds in patients with functional disorders. METHODS: We studied 157 consecutive patients who had undergone extensive diagnostic work-up to exclude organic disease. Abdominal symptoms were assessed with a validated instrument, and patients were categorized as having functional dyspepsia, IBS, or both. With a barostat device, we tested small intestinal mechanosensitive function in 22 randomly selected patients from this population (with functional dyspepsia, IBS, or both) and 22 healthy controls. RESULTS: Sixty-seven patients (43%) reported simultaneous symptoms of functional dyspepsia and IBS, whereas symptoms of functional dyspepsia or of IBS alone occurred in 68 (43%) and 22 (14%) patients, respectively. Thresholds for first perception and maximum tolerated pressure (mm Hg +/-SD) were significantly lower in patients (21.0 +/- 2.0 and 31.0 +/- 1.0) than in controls (32.0 +/- 1.8 and 39.0 +/- 0.9, p < 0.001). However, thresholds for first perception and maximum tolerated pressure did not differ (p > 0.6) in patients with functional dyspepsia alone (20.1 +/- 3.2 and 28.9 +/- 2.5, n = 9), functional dyspepsia and concomitant IBS (19.9 +/- 2.7 and 30.7 +/- 2.2, n = 8), or IBS alone (23.5 +/- 2.3 and 33.3 +/- 3.0, n = 5). CONCLUSIONS: Small intestinal mechanosensitive pathways are disturbed in patients with functional dyspepsia and IBS. Differences in the pattern and localization of symptoms probably do not reflect differences in small intestinal sensory thresholds. Functional dyspepsia and IBS cannot be distinguished on the basis of altered small intestinal sensory thresholds.     

Psychosocial aspects of assessment and treatment of irritable bowel syndrome in adults and recurrent abdominal pain in children.

This article presents a selective review of psychosocial research on irritable bowel syndrome (IBS) in adults and on a possible developmental precursor, recurrent abdominal pain (RAP), in children. For IBS the authors provide a summary of epidemiology, of the psychological and psychiatric disturbances frequently found among IBS patients, and of the possible role of early abuse in IBS. A review of the psychosocial treatments for IBS finds strong evidence to support the efficacy of hypnotherapy, cognitive therapy, and brief psychodynamic psychotherapy. The research relating RAP to IBS is briefly reviewed, as is the research on its psychological treatment. Cognitive-behavioral therapy that combines operant elements and stress management has the strongest support as a treatment for RAP. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sensory dysfunction in fibromyalgia patients with implications for pathogenic mechanisms

This study, addressing etiologic and pathogenic aspects of fibromyalgia (FM), aimed at examining whether sensory abnormalities in FM patients are generalized or confined to areas with spontaneous pain. Ten female FM patients and 10 healthy, age-matched females participated. The patients were asked to rate the intensity of ongoing pain using a visual analogue scale (VAS) at the site of maximal pain, the homologous contralateral site and two homologous sites with no or minimal pain. Quantitative sensory testing was performed for assessment of perception thresholds in these four sites. Von Frey filaments were used to test low-threshold mechanoreceptive function. Pressure pain sensitivity was assessed with a pressure algometer and thermal sensitivity with a Thermotest. In addition the stimulus-response curve of pain intensity as a function of graded nociceptive heat stimulation was studied at the site of maximal pain and at the homologous contralateral site. FM patients had increased sensitivity to non-painful warmth (P < 0.01) over painful sites and a tendency to increased sensitivity to non-painful cold (P < 0.06) at all sites compared to controls, but there was no difference between groups regarding tactile perception thresholds. Compared to controls, patients demonstrated increased sensitivity to pressure pain (P < 0.001), cold pain (P < 0.001) and heat pain (P < 0.02) over all tested sites. The stimulus-response curve was parallely shifted to the left of the curve obtained from controls (P < 0.003). Intragroup comparisons showed that patients had increased sensitivity to pressure pain (P < 0.01) and light touch (P < 0.05) in the site of maximal pain compared to the homologous contralateral site. These findings could be explained in terms of sensitization of primary afferent pathways or as a dysfunction of endogenous systems modulating afferent activity. However, the generalized increase in sensitivity found in FM patients was unrelated to spontaneous pain and thus most likely due to a central nervous system (CNS) dysfunction. The additional hyperphenomena related to spontaneous pain are probably dependent on disinhibition/facilitation of nociceptive afferent input from normal (or ischemic) muscles.     

Psychological factors in illness and recovery

To review evidence that psychological factors affect the course of physical illness three areas are examined: epidemiological evidence showing the levels of psychiatric disturbance co-morbid with physical illness; health services research showing the burden of disease and care associated with this co-morbidity; randomised, controlled trials of psychological interventions in cancer, myocardial infarction and irritable bowel syndrome. There is substantial psychiatric co-morbidity with physical illness which is associated with increased disability, mortality and utilisation of health-care resources (primary care visits, hospitalization, length of hospital stay, cost). A small number of controlled intervention studies have shown the efficacy of psychological interventions to prolong survival in cancer and myocardial infarction, and to improve symptomatology in irritable bowel syndrome and other chronic somatizing conditions. Psychological factors do significantly affect outcomes of physical illness. The role of psychological treatments, alongside somatic therapies, needs further study.     

Is functional dyspepsia just a subset of the irritable bowel syndrome?

To determine whether functional dyspepsia and irritable bowel syndrome are different entities, epidemiological data, factor analysis studies, physiological data and associated psychological symptoms were reviewed. Between 30% and 60% of patients with either diagnosis also meet the criteria for the other diagnosis, a level greater than expected to occur by chance but not sufficient to infer an identity. Most factor analysis studies identify independent clusters of symptoms corresponding to functional dyspepsia and irritable bowel syndrome. Visceral hypersensitivity is seen throughout the gastrointestinal tract in both disorders, but the motility patterns seen in association with functional dyspepsia (principally antral hypomotility and delayed gastric emptying) differ from the motility patterns seen in irritable bowel syndrome. Psychological symptoms are similar in these two disorders but are not believed to be aetiological for either of them. Thus, based on a factor analysis of gastrointestinal symptoms and differences in intestinal motility, functional dyspepsia and irritable bowel syndrome appear to be different entities.     

Acid infusion does not affect intraesophageal balloon distention-induced sensory and pain thresholds

OBJECTIVE: We sought to evaluate the potential interaction between acid-sensitive chemoreceptors and pressure-sensitive mechanoreceptors. METHODS: Twenty-one normal control subjects underwent esophageal balloon distention with a commercially produced combined-manometry, acid-infusion, balloon-distention catheter. The intraesophageal balloon was localized 10 cm above the lower esophageal sphincter. With a mechanical pump, sensory and pain thresholds were determined by using sequentially increasing balloon volumes (range 0-23 cc, increment 1 cc). A 15-min acid infusion (0.1 N HCl at 6-8 cc/min) or a 0.9 N saline infusion was then applied just proximal to the distending balloon, followed by a second determination of sensory and pain thresholds. The results of the trials before and after acid and placebo were compared. RESULTS: All subjects tolerated the procedure. The initial mean volume-to-sensory threshold was 9.1 ml (range 5-16), decreasing to 6.2 (range 4-11) after acid infusion (p < 0.005). The sensory threshold also decreased from 9.8 ml (range 6-16) to 6.8 ml (range 4-14) after saline infusion (p = 0.06). The mean volume-to-pain threshold was 16.0 (range 14-21) before and 15.2 (range 11-23) after acid infusion and 15.8 (range 12-20) before and 14.0 (range 10-20) after saline infusion (NS). CONCLUSION: We conclude that infused acid has no effect on pain threshold and has a nonspecific effect on sensory threshold induced by esophageal balloon distention.     

Acoustic neuroma surgery and delayed facial palsy

The Prader-Willi syndrome (PWS) is associated with a tendency to self-injury and a reduced sensitivity to painful stimuli. Somatosensory functions were studied in 5 children aged 11-13 years with PWS. Tactual perception in the hands (stereognosis) was apparently normal in 4 of them. Sensory nerve conduction velocities in the median nerve and latencies for sensory evoked potentials were similar in the PWS subjects and in 10 healthy controls indicating a preserved myelinisation of sensory nerve fibers in PWS. Sensory nerve action potential amplitudes in the PWS group were on an average only 40-50% of normal size (p = 0.03), suggesting a reduced number of normal axons in the median nerve. The results may be relevant for the impaired pain sensitivity in PWS because similar neurographic findings and a low density of peripheral nerve fibers have been reported in patients with hereditary or congenital insensitivity to pain.     

Pain and pain control.

The past few years have seen a renewed and burgeoning interest in pain and its control. Whereas in previous years emphasis had been placed mainly on the sensory aspects of pain, recent approaches have viewed pain as a complex phenomenon composed of both sensory and motivational dimensions. Control of acute and chronic pain often involves dealing with the motivational aspects of pain perception rather than with the sensory components. Psychological variables play a key role in this effort. This article reviews the major theories of pain perception and the relevance of psychological variables, the important area of pain measurement, the correlates of pain perception, and the major behavioral attempts at manipulating pain perception. (7 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Homeopathic medicine and presidential health: homeopathic influences upon two Ohio presidents

Forty-five diabetes patients with painful peripheral polyneuropathy were enrolled in a 3-month observational study comparing the therapeutic efficacy of Milgamma tablets (50 mg benfothiamine and 0.25 mg cyancobalamine) with parallel randomized treatment assignment with the conventional vitamin B complex treatment regimen Neurobex. Thirty patients in group one were randomized to receive two Milgamma tablets qid for three weeks followed by 1 Milgamma tablet tid for 9 weeks. In group two 15 patients received two Neurobex tablets tid for the entire 3-month study period. Therapeutic efficacy was assessed on the basis of within-patient differences in pain severity between Milgamma and Neurobex-treated patients and in vibration perception thresholds using the Rydel-Seiffer biothesiometer at baseline and at the end of the study. Statistically significant relief of both background and peak neuropathic pain was achieved in all of the Milgamma-treated patients and vibration perception thresholds dramatically improved with a median of 1.56 measured on the biothesiometer scale (t = 3.24, P < 0.01). The sensory symptoms improvement was insignificant in the Neurobex-treated patient group and the changes in the vibration perception thresholds failed to reach statistical significance. The therapeutic efficacy of Milgamma was greater in patients with early-stage diabetes as compared with those with advanced diabetic neuropathy. No adverse reactions were observed following the administration of the medication. Our results underscore the importance of Milgamma tablets as an indispensable element in the therapeutic regimen of patients with painful diabetic polyneuropathy.     

Changes in pain perception after treatment for chronic pain

Pain threshold, sensitivity, response bias and ability to discriminate were measured before and after treatment for 15 improved and 15 unimproved chronic pain patients diagnosed as having myofascial pain dysfunction (MPD) syndrome, There were no differences between the groups before treatment. After treatment, the improved group showed an increase in pain threshold, sensitivity and ability to discriminate between different levels of painful stimulation and a decrease in response bias to report pain. The unimproved group showed no changes.     

Functional gut disorders: from motility to sensitivity disorders. A review of current and investigational drugs for their management

Functional gut disorders include several clinical entities defined on the basis of symptom patterns (e.g., functional dyspepsia, irritable bowel syndrome, functional abdominal pain, functional abdominal bloating), for which there is no established pathophysiological mechanism. Because there is no well-defined pathophysiological target, treatment should be aimed at symptom improvement. Prokinetics and antispasmodics have been widely used in the treatment of functional gut disorders on the assumption that disordered motility is the underlying cause of symptoms, and symptom improvement is indeed achievable with these compounds in some, but not all, patients with features of hypo- or hypermotility, respectively. In the first part of this review, we cover the basic pharmacology and discuss the rationale for the clinical use of prokinetics and antispasmodics. On the other hand, in the past few years, the explosive growth in the research focusing on visceral sensitivity and visceral reflexes has suggested that at least some patients with functional gut disorders have altered visceral perception. Thus, the second part of the review covers these developments and focuses on studies addressing the issue of drugs modulating visceral sensitivity.     

Signal detection and threshold measures for chronic back pain patients, chronic illness patients, and cohort controls to radiant heat stimuli.

15 chronic low back pain patients, 11 chronic respiratory patients, and 11 nonpatient controls (mean ages 47–56 yrs) were studied using a standard radiant heat signal detection methodology. Following determination by ascending limits of each S's stimulus detection and faint pain thresholds, 26 randomized trials at each of 5 stimulus levels were administered. Ss rated each stimulus on a 6-point subjective rating scale ranging from no pain to severe pain. Results indicate that the back pain Ss and respiratory Ss had higher radiant heat pain thresholds than the controls, and the back pain Ss had a discrimination deficit for mildly painful stimuli. Results fit the predictions of an adaptation model of pain perception in chronic pain patients as opposed to a hypochondriasis model. (9 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Investigations for chronic pelvic pain

Chronic pelvic pain (CPP) is a common problem with a prevalence of about 38/1000 among women aged 20–50 years. The main gynaecological diagnoses include endometriosis, pelvic inflammatory disease and adhesions. The most common gastrointestinal diagnosis is irritable bowel syndrome and genitourinary diagnosis includes pathology such as interstitial cystitis. It is a challenge instigating the right investigations for patients with chronic pelvic pain because there is a considerable symptom overlap. They also have a higher prevalence for symptoms such as dysmenorrhea and dyspareunia. In this review, we aim to discuss the clinical consultation necessary to help us decide upon which investigative tools we need to use to help diagnose the cause(s) of CPP, although one needs to stress that a specific cause may not be found in patients with CPP and symptom focused multidisciplinary management of CPP is at least as important as diagnosis of specific pathology and disease focused treatment.     

Current principles of multidisciplinary treatment of pain in orthopedic clinics

Differentiated strategy of treating patients with acute and chronic pain is developed. Preemptive analgesia is a priority trend in the treatment of acute postoperative pain. The most prevalent method of postoperative analgesia is prolonged opioid epidural analgesia carried out in intensive care wards and other wards by an acute pain management team. For treating patients with chronic painful syndromes, protocols of initial clinical and diagnostic evaluation are developed, permitting the choice of individual treatment strategy. Differentiated complex drug therapy planned with consideration for individual course of the painful syndrome is the basis of treating patients with phantom pain syndrome. Algorithms of differentiated therapy of radicular and spondylogenic pain are designed. Stage-by-stage analysis of treatment efficacy is carried out using modern electrophysiological methods. Realization of the proposed organization principles improved the efficacy of postoperative analgesia to 88.2%, prevented the development of postoperative painful syndrome in 35.6% cases, decreased the incidence of phantom pain syndrome after amputation of the limb from 63.3 to 31.6% and increased the efficacy of this syndrome treatment to 70.1%, and increased the efficacy of treating vertebrogenic painful syndromes to 82.3%.     

Expression of multidrug resistance (mdr) gene(s) in primary lymphoid organs of chicken immune system during embryonic development

The present study investigated the processing of painful electrical stimuli in patients with unilateral frontal or parietal lobe damage and matched control subjects. Patients with frontal lesions showed increased pain thresholds when the stimuli were administered contralateral to the lesion. While the peak-to-peak amplitudes of the N150/P250 components of the somatosensory potentials increased linearly with stimulus intensity in the control subjects, the responses in the frontal group did not change significantly between stimulation at pain and tolerance threshold. There was no evidence for altered pain processing in patients with parietal lobe lesions. The findings of the present study support the hypothesis of an involvement of the frontal cortex in pain perception in humans.     

Sexual and physical abuse in women with fibromyalgia: association with outpatient health care utilization and pain medication usage

OBJECTIVE: To evaluate the relationship between sexual and/or physical abuse and health care usage in patients with fibromyalgia (FM) and identify variables that may influence this relationship. METHODS: We assessed history of sexual/physical abuse, health care utilization, and medication usage, as well as related variables in 75 women with FM using standardized questionnaires, structured interviews, and laboratory pain perception tasks. RESULTS: Fifty-seven percent of FM patients reported a history of sexual/physical abuse. Compared to non-abused patients, abused patients reported significantly greater utilization of outpatient health care services for problems other than FM and greater use of medications for pain (P < or = 0.025). Consistent with our expectations, abused patients also were characterized by significantly greater pain, fatigue, functional disability, and stress, as well as by a tendency to label dolorimeter stimuli as painful regardless of their intensities (P < or = 0.05). Additional analyses suggested that the high frequency of sexual/physical abuse in our patients was associated primarily with seeking health care for chronic pain rather than the FM syndrome itself or genetic factors. CONCLUSION: There is an association in FM patients between sexual/physical abuse and increased use of outpatient health care services and medications for pain. This association may be influenced by clinical symptoms, functional disability, psychiatric disorders, stress, and abnormal pain perception. The relationships among these variables should be further tested in prospective, population-based studies.