Biomedical subjects
Publications and source records attributed to D Yarnitsky.
Quantitative sensory testing (QST) has been used clinically for the last two decades, yielding a substantial number of publications regarding these applications. In this review we tried to amass together the major findings of these publications into one monograph, excluding those dealing with pain. This was done with the aim of assisting clinicians in the better use of QST techniques for the benefit of their patients.
Smooth muscle electromyographic (EMG) recording from the corpora cavernosa is a potentially useful clinical tool for the diagnosis of impotence. Controversy still exists regarding the nature of this signal, which could be resolved using animal models. The signal recorded from denuded rat corporal surface was Fourier transformed, and power at 0.01-1 Hz was calculated. Measurements were taken in the flaccid state and during erection induced by intracorporal injection of smooth muscle relaxants [the phosphodiesterase inhibitors papaverin and isobutylmethylxanthine (IBMX)]. Recorded activity decreased significantly during the pharmacologically evoked erection: the mean square root power of 250.7+/-137.1 microV decreased to 49.8+/-14.1 microV (P<0.0001) after papaverin, and IBMX caused it to decrease from 222.8+/-132.0 microV to 58.1+/-40.8 microV (P<0.0001) (mean +/- SD). Intracorporal injection of adrenaline partially reversed the response, increasing activity to 135.3+/-72.3 microV (P=0.01) and 137.5+/-122.6 microV (P=0.015), respectively, in parallel with detumescence. In order to rule out a mechanical artefactual explanation for these results, recording was also performed before and during artificial erection induced by the intracorporal infusion of saline. This manipulation did not cause any change in corporal activity, despite corporal engorgement and increased pressure. In conclusion, the signal indeed reflects changes in the tone of corporal smooth muscle, and therefore should be regarded as a genuine EMG recording.
OBJECTIVE: The P300 component of event-related potentials is affected by personal meaningfulness of the stimulus to the subject. Thus, the P300 component could provide an objective parameter in the emotional assessment of road accident mild head injury patients, when exposed to relevant stimuli. METHODS: Thirteen patients with post-traumatic symptoms and 14 healthy controls were evaluated in this study. Two word types, distinguished by color, were presented on a computer screen in active 'oddball' paradigm conditions. In the first subtest, the targets were accident-related (stressful) words; in the second subtest, the targets were non-accident-related (neutral) words. Target (20%) and non-target (80%) were defined by word color. Data recorded from Pz were analyzed for P300 parameters. RESULTS: Patients and controls differed in their reaction to word types (group x word main effect P = 0.0089), regardless of the oddball presentation. Overall, accident-related words produced a significantly larger P300 wave than neutral words in patients (P = 0.0001), but not in controls (P = 0.5741). Significant correlation was found between combined P300 amplitude difference (all stressful words vs. all neutral words) and the patient's Zung state anxiety score (r = 0.68, P = 0.01). CONCLUSION: We suggest the P300 component can provide a useful, objective tool in the assessment of mild head injury patients.
Neuropathic pain is often severe, persistent, and responds poorly to analgesic medications. Recent evidence suggests that N-methyl-D-aspartate (NMDA) receptor antagonists may be effective in the treatment of neuropathic pain. The present trial was designed to test the efficacy of acute administration of the NMDA receptor antagonist amantadine in relieving surgical neuropathic pain in patients with cancer. The study sample consisted of 15 cancer patients with the diagnosis of surgical neuropathic pain. Two 500 ml infusions of either 200 mg amantadine or placebo were administered over a 3 h period, in a randomized order, 1 week apart from each other. Spontaneous and evoked pain were measured for 48 h before treatment, during treatment, and for 48 h following treatment. An average pain reduction of 85% was recorded at the end of amantadine infusion vs. 45% following placebo administration. The difference in pain relief between the two treatments was statistically significant (P = 0.009). Mean pain intensity remained significantly lower during the 48 h following amantadine treatment as compared with the 48 h prior to treatment (31% reduction; P = 0.006), whereas no such effect was found with the placebo (6% reduction; P = 0.40). Amantadine, but not the placebo, also reduced 'wind up' like pain (caused by repeated pinpricking) in four patients. We conclude that amantadine infusion is a safe and effective acute treatment for surgical neuropathic pain in cancer patients. Further trials with long-term oral or parenteral amantadine treatment should be conducted.
A double-blind, randomized, placebo-controlled trial was conducted to study the analgesic efficacy of the NMDA (N-methyl-D-aspartate) receptor antagonist memantine (1-amino-3,5-dimethyladamantane hydrochloride) in relieving postherpetic neuralgia (PHN). Memantine (or an identical-looking placebon=12/group) was administered at a dose of 10 mg/day for one week, and 20 mg/day for an additional 4 weeks. All patients were required to record their pain level twice daily during the entire study period, with the use of a 0-10 numerical pain scale (NPS). The McGill Pain Questionnaire (MPQ), spontaneous pain, and a series of mechanical and thermal stimuli-induced pain were measured with the use of a 0-100 visual analogue scale (VAS), on six office visits. Quantitative thermal testing (QTT) and routine blood tests were performed at the beginning and at the end of the study. Although reduction in spontaneous pain, mechanical and cold allodynia, mechanical hyperalgesia, and < > like pain were found in both groups, there were no significant differences between memantine and the placebo on any of the outcome measures. No changes were found in either group in MPQ scores or in quantitative thermal thresholds. Although three patients were withdrawn from the memantine group and only one from the control group, no differences in incidence of adverse effects between the two groups were found. Study results show that memantine is ineffective in reducing spontaneous and evoked pain in patients with PHN. Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain.
An open trial was conducted to study the potential efficacy of lamotrigine, a novel antiepileptic agent that blocks voltage-sensitive sodium channels and inhibits the release of glutamate, in relieving the pain associated with diabetic neuropathy. Subsequent to a 1 week washout period from previous analgesics, lamotrigine was administered at a dose of 25 mg/day for 1 week. The dose was doubled on a weekly basis up to 400 mg/day over 6 weeks. The McGill pain questionnaire (MPQ), spontaneous pain and a series of mechanical and thermal stimuli-induced pain were measured with the use of 0-100 visual analogue scale (VAS), on seven office visits. Pain level was also recorded by each patient twice daily, 1 week before, during, and 2 weeks after the treatment period with the use of a 0-10 numerical pain scale (NPS). Quantitative mechanical (Von Frey filaments) and thermal testing (QTT), and routine blood tests were performed at the beginning and at the end of the study. Thirteen patients completed the study. Spontaneous pain measured by VAS and NPS gradually dropped from a baseline of 49 +/- 8 and 6.8 +/- 0.6, to 20 +/- 8.6 (p < 0.001) and 4.3 +/- 0.9 (p < 0.001), respectively, at the end of the treatment period. Similarly, cold allodynia dropped from 38 +/- 9.2 to 16 +/- 15.3 (p = 0.01), and the MPQ score from 13.6 +/- 0.8 to 11.0 +/- 1.5 (p < 0.01). In contrast, no significant changes were found in the QTT, mechanical pain thresholds and laboratory results. Two patients were withdrawn from the study because of adverse effects. A long-term follow up showed that most patients were still using lamotrigine 6 months after the end of the study. The results of the study suggest that lamotrigine is potentially effective and safe in treating painful diabetic neuropathy. Copyright Rapid Science Ltd
5-Fluorouracil (5-FU) is known to cause multifocal cerebral demyelination, which is pathologically related to a central inflammatory demyelinating process. To date, no case of peripheral neuropathy has been described after the administration of 5-FU alone. The authors describe two patients who had peripheral neuropathy that developed while they were receiving 5-FU-based chemotherapy.
Quantitative sensory testing has become commonplace in clinical neurophysiology units. Measurement of the thermal and vibratory senses provides an estimate on function of sensory small and large fibers, respectively. Being psychophysical parameters, sensory threshold values are not objective, and various test algorithms have been developed aiming at optimized results. In this review the various test algorithms are screened, and their relative advantages and disadvantages are discussed. Considerations of quality control are reviewed, and the main fields of clinical application are described.
Electrical signals recorded from the penis have been suggested as reflecting electromyographic activity in the underlying smooth muscles. In order to verify this assertion, we manipulated the signal recorded from rat urethra surface. Stimulation of the pelvic nerve brought about a reduction of activity (965 +/- 826 to 166 +/- 143 microV, root mean square of the power at range 0.005-1 Hz, P = 0.008), with a significant frequency-response relationship (P = 0.0002). This effect was not altered by temporary closure of the aorta (P = 0.89), thus ruling out hemodynamic artifact as a possible cause of signal change during stimulation. Our findings support the assertion that the signal indeed reflects activity in smooth muscle.
Spatial summation of thermal pain crosses dermatomal boundaries. In this study we examined whether a vibrational stimulus applied to adjacent or remote dermatomes affects thermal pain perception to the volar forearm. Contact heat at 2 degrees C above thermal pain threshold was applied, and a Visual Analog Scale (VAS) was used for pain assessment. We found a significant decrease in mean VAS rating when simultaneous vibratory stimuli were given to the dermatome adjacent to that receiving thermal stimulation, or to the same dermatome on the contralateral side. There was no change in VAS rating when vibration was given two or more dermatomes away. Vibration within the same dermatome also did not yield a significant change in VAS rating, possibly due to difficulty in magnitude assessment of stimuli given simultaneously within a single dermatome. The finding that vibration can reduce pain across dermatomes may allow for more flexible design of stimulation therapy for pain.
A prospective study was designed to determine which patients with carpal tunnel would respond to conservative therapy (splinting and local injection of corticosteroids). The study included 50 hands of 34 patients, aged 25-80 years, with a mean follow-up of 18 months. Conservative therapy was effective in 82% of hands after 8 weeks, but symptoms subsequently recurred, so that by the end of a year only 20% remained asymptomatic. Failure of conservative therapy was predicted by long duration of symptoms, older age, permanent paresthesia, 2-point discrimination threshold above 6 mm, positive Phalen test within 30 seconds, and long motor and sensory distal latency.
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The incidence of carpal tunnel syndrome is increased during pregnancy. The common conventional therapeutic approach is conservative, as symptoms usually abate after delivery. We describe our experience with 65 hands (50 patients), who were treated initially by a conservative approach and later, when required, surgically. We found that all patients who (i) had either started having CTS symptoms during the first two trimesters or had previous history of CTS symptoms; and (ii) had both a positive Phalen test within less than 30 seconds and abnormal two point discrimination at the finger tips ( > 6 mm), were eventually operated upon, either during or after pregnancy, as conservative measures failed. We therefore recommend consideration of an early surgical approach in patients fulfilling these criteria.
Pain evoked potentials (EPs) have been used in the last two decades as means of obtaining objective measures of pain, in clinical and experimental setups. The possibility that the pain EP wave contains elements of the endogenous P300 potential rather than being a neurophysiological correlate of pain has been raised by a number of authors, but the issue has not been resolved. In this study, two experiments were performed to study the effect of nonmodality-specific factors on the laser EP: (1) a stimulus attend as opposed to a stimulus-ignore condition and (2) counterbalanced oddball and task P300 stimulus presentations. The latter was to permit full examination of the separate and combined influences of each condition on the EP. Stimuli were given to the radial hand of 10 healthy volunteers using a CO2 laser. The positive component of the laser EP was affected by both manipulations relating to (1) attention (P = 0.0146) and (2) the frequency condition (P = 0.003) in the P300 paradigm. The task condition in the second paradigm did not affect the positive wave on its own, although its effect was visible in interaction with frequency (P = 0.033). In conclusion, although the presence of a somatic component in the laser EP cannot be rules out, we suggest that the laser EP contains a definite non-modality-specific P300 component, and is not a pure neurophysiological correlate of pain intensity.
Experimental heat pain transients were administered to 30 normal volunteers over four weekly sessions, measuring both heat pain (HP) threshold and suprathreshold magnitude estimation through VAS. Repeatability and bias for these two factors were evaluated. Heat pain thresholds measured through the method of limits were previously shown to have inter-session bias, presumably due to a practice effect. Existence of such a bias between first and second measurement sessions casts doubt on the usefulness of this parameter for pain assessment of individuals over time. In the present study, measurements of normal HP thresholds over four sessions showed that bias exists between the first and successive sessions, but not among sessions other than the first. It is concluded that (i) HP thresholds obtained from a single session are of limited value, and should be carefully interpreted. (ii) Long-term studies that use the HP threshold should take results from the second (or later) session as their baseline. The Visual Analog Scale (VAS) is considered the 'gold standard' for assessment of clinical and suprathreshold experimental pain, and changes in VAS score are regarded as significant evidence of individual response to treatment, placebo, or experimental manipulation. Although its overall group accuracy and precision have been examined for both clinical and experimental pain, and found adequate (Price 1988), the VAS has not been rigorously assessed for repeatability. Stimuli at three pain levels, 1.5, 3 and 4.5 degrees C above each individual's heat pain threshold as determined at each session, were given. Several models of analysis of the VAS were tested and repeatabilities (r) obtained from these analyses demonstrate poor precision for each of the tested analysis models. For example, inter-session repeatabilities for the three individual pain levels ranged from r = 3.8-4.7, effectively providing a confidence interval of 7.6-9.4 for any VAS reading on a 0- to 10-point scale. An examination of intra-session VAS provided somewhat better results. Thus, use of the VAS in similar experimental settings is called into question. The use of the VAS in clinical settings, where individual assessments are necessary, is also called into question, but remains to be specifically tested.
PURPOSE: To our knowledge no direct measurement of autonomic failure in the penis is currently available. Indirect techniques in clinical use, such as bulbocavernosus reflex, genital somatosensory evoked potentials and biothesiometry, all rely on large nerve fiber function. Since micturition and potency depend on small fibers of the peripheral system, tests of these fibers might be more relevant in the clinical diagnostic evaluation. We provide upper normal limits and demonstrate repeatability of small fiber mediated sensations of warm and cold sensory thresholds on penile skin. MATERIALS AND METHODS: Penile warm and cold sensory thresholds were measured in 35 healthy volunteers (at 2 sessions in 27) via 2 methods. RESULTS: Upper normal values, expressed as 95% confidence limits for warm and cold thresholds, through methods of limits and levels as well as inter-session repeatability are given. CONCLUSIONS: Penile thermal thresholds are repeatable and can be used as a valid diagnostic tool to assess somatic small fiber function in patients with lower urinary tract disorders.
Three hundred and forty-one consecutive impotent patients were evaluated for the presence of polyneuropathy (PNP) by neurophysiological and psychophysical tools, including nerve conduction and quantitative sensory tests (thermal and vibratory). PNP was present in 38% of diabetics, and 10% of non diabetics. Overall, PNP was found in 19% of impotent patients. PNP is relatively common among impotent patients, and might play a causative role. Patients judged 'neurogenic' and those judged 'vasculogenic', based on nocturnal tumescence test (NPT) and vasoactive drug injection tests, had very similar rates of PNP (21 and 23%, respectively). Thus it is suggested that the vasoactive drug injection test does not serve in discriminating neurogenic from non-neurogenic impotence. NPT, however, faithfully discriminates psychogenic from organic impotence, as far as PNP is involved, since a very low percentage of patients with normal NPT had PNP.
Cerebral evoked potentials (EPs) in response to painful stimuli have been recorded since the 1970s. Based on the apparent relationship of the response amplitude to intensity of stimulation, these potentials are conventionally interpreted as reflecting the sensory-discriminative aspects of pain. As such, pain-EPs provide an objective measure for sensation of pain. An alternative interpretation regards the pain-EP as comprised of at least two overlapping components, one pain-specific, the other, a P300 wave. In the case of pain, the P300 may reflect the degree of discomfort or unpleasantness, thus reflecting the emotional-motivational aspect. To establish the nature of the pain-EP, mini doses of a benzodiazepine, counterbalanced with placebo, were given to 6 normal volunteers. Benzodiazepines decrease anxiety, and so diminish the emotional response to pain, but they have no analgesic effect. In all subjects, pain perception was unchanged, while the EP wave was almost completely obliterated. We conclude that the pain-EP reflects the emotional-motivational response to pain rather than the sensory-discriminative. Thus, it provides a useful neurophysiological tool for studying the emotions associated with pain.