European Journal of Pain 10 (2006) 467–471 www.EuropeanJournalPain.com
Decreased sensitivity to experimental pain in adjustment disorder Karl-Ju¨rgen Ba¨r *, Stanislaw Brehm, Michael Karl Boettger, Gerd Wagner, Silke Boettger, Heinrich Sauer Department of Psychiatry, Friedrich-Schiller-University of Jena, Philosophenweg 3, 07743 Jena, Germany Received 12 January 2005; received in revised form 12 June 2005; accepted 6 July 2005 Available online 11 August 2005
Abstract An altered perception of pain has been described for several psychiatric disorders. To date the influence of adjustment disorders (AD) on pain perception has not been described. Here, we investigated perception of experimentally induced pain in 15 patients suffering from AD (subtype with depressive symptoms) and controls matched for age and sex. Thresholds and tolerances were assessed for thermal and electrical pain on both sides of the body. We found an overall increase of pain thresholds and tolerances in AD patients as compared to controls, predominately on the right side of the body. Analogue findings have been reported for pain perception in major depressive disorder (MDD). Of the data obtained, only thermal pain threshold on the right arm correlated with the severity of depressive symptoms. Although the underlying pathology is elusive it is likely that the mechanisms for reduced pain sensitivity are comparable in MDD and AD. 2005 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved. Keywords: Adjustment disorder; Pain; Lateralization; Thermal; Sensory; Stress; Psychiatric assessment
1. Introduction Several previous reports have focused on different interactions between perception of pain and psychiatric disorders (for review, see Lautenbacher and Krieg, 1994). Patients suffering from a major depressive disorder (MDD) have especially been investigated, as they present with a high rate of clinical pain complaints and show a decreased sensitivity to experimental pain (Lautenbacher et al., 1999; Corruble and Guelfi, 2000; Dickens et al., 2003; Ba¨r et al., 2005). Furthermore, the increase in pain thresholds is apparently more prominent in women and is most pronounced * Corresponding author. Tel.: +49 3641 935282; fax: +49 3641 936217. E-mail address:
[email protected] (K.-J. Ba¨r).
on the right side of the body (Ba¨r et al., 2003; Spernal et al., 2003). To date, the influence of psychiatric disorders induced by an external stressor on pain thresholds is unknown. One example of stress-induced psychiatric disorders is the adjustment disorder (AD), which is characterized by the development of affective or behavioral symptoms. Stressors can be natural disasters (e.g. earthquake), major life events (e.g. development of a medical disorder), or interpersonal problems (such as divorce). The affected person displays either marked distress, or impairment in functioning (e.g. inability to work). Here, thresholds and tolerances towards electrical and thermal pain were assessed. All AD patients included in this study suffered from a subtype presenting with depressed mood (DSM-IV, 309.0) and were investigated within days after the onset of symptoms. Rating
1090-3801/$32 2005 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ejpain.2005.07.001
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2.2. Pain testing
scales for depression were correlated with pain parameters.
Pain tests were performed in a quiet room which was kept comfortably warm (22–24 C). The protocol included tests for thermal and electrical pain thresholds. The order of tests was pseudorandomized across subjects. The first subject underwent thermal pain testing first followed by electrical pain tests. This order was changed for the second subject et cetera. Similarly, the order of the side tested first was counterbalanced and pseudo-randomized across subjects. The first subject in each test was tested on the right arm first and then on the left. The order was then changed for every consecutive subject. The test was discontinued when participants reached the maximum tolerance levels permitted (e.g. 53 C, 9.99 mA). In these cases the maximum tolerance levels were used as tolerance score.
2. Materials and methods 2.1. Subjects Fifteen right-handed patients suffering from AD with depressed mood and 15 control subjects matched with respect to age, gender, handedness and education (see Table 1) were investigated. All patients had experienced an interpersonal crisis that occurred up to three days prior to admission. For this reason they were admitted to our hospital for a brief psychiatric intervention. None of them was taking any medication which may have interfered with pain testing such as antidepressants or analgesics. All control subjects were recruited among hospital employees and medical students. Diagnosis of AD was established according to DSM-IV criteria using the structured clinical interview for DSM-IV (SCID; First et al., 1997). Depressive symptoms were assessed using the Hamilton depression rating scale (21 item HAM-D, (Hamilton, 1960)). Participants gave written informed consent to a protocol approved by the Ethics Committee of the Medical Faculty of the FriedrichSchiller-University, Jena. All tests were performed between 4 and 8 p.m. Patients and controls were asked to refrain from smoking, eating, drinking coffee or exercise for the last two hours prior to the investigation. Due to their inpatient status no patients had access to alcohol 24 h prior to assessment. Controls were asked to avoid any alcohol for a similar period prior to assessment. Patients and control subjects with a clinical history of preexisting or present psychiatric disorders (e.g. major depression), patients with other subtypes of AD, hypertension, diseases associated with altered blood clotting, peripheral neuropathies, upper limb trauma, any drug intake within the last 48 h as well as alcohol dependency were excluded from the study. Data on the average amount of alcohol consumption per week was not obtained.
2.2.1. Thermal pain Thermal pain threshold (TPT) and thermal pain tolerance (TPTO) were determined by an ascending method of limits, using a 9 cm2 contact thermode with a temperature increase of 0.5 C/s (baseline temperature: 32.0 C; maximal temperature: 53.0 C) as previously described (Ba¨r et al., 2003). The thermode was attached to the left or right volar wrist. To determine thermal pain threshold, subjects were asked to read the following written instruction: ‘‘When thermal perception becomes painful press the stop button immediately’’. Three learning trials were followed by five consecutive tests for thermal pain threshold. Following the investigations for thermal pain threshold on one hand thermal pain tolerance was investigated. Similarly, subjects were instructed to press the stop button when the temperature became intolerable. Again, after three learning trials five tests were performed and averaged. 2.2.2. Electrical pain Electrical pain threshold (EPT) and tolerance (EPTO) were measured using the commercially available Neurometer CPT/C (CPT = Current Perception Thres-
Table 1 Demographic data of participants AD
Controls
Participants
n = 15; female: 13
n = 15; female: 13
Demographic data (mean ± SD) Age (years) Age of females (years) Secondary school degree Employed Unemployed/inability to work Disease duration in days Smokers
36.0 ± 12.5 36.6 ± 13.1 n = 15 n=9 n=6 2–3 n=6
36.1 ± 12.0 36.8 ± 12.4 n = 15 n = 11 n=4
Hamilton depression rating scale
15.7 ± 3.6
2.1 ± 1.4
n=5
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hold, Neurotron, Inc., Baltimore, USA) automated electrodiagnostic device. A pair of 1 cm diameter gold electrodes were coated with an electroconductive gel and taped to the distal phalange of the left or right index finger. Thresholds were determined by means of a 5 Hz stimulus. Pain threshold testing was performed using a standardized automated double-blind methodology (Neurometer CPT/C Operating Manual, Neurotron Inc, 1999). The stimulus was presented with increasing intensity ranging from 0 to 9.99 mA as long as the subjects pressed a so-called ‘‘Test Cycle’’ button. Subjects were instructed to release the button when they perceived the stimulus as painful (EPT) and intolerable (EPTO), respectively. Tests were repeated three times and averaged. The reliability of pain threshold measures using the Neurometer CPT/C device has been documented in several recent studies (Gustorff et al., 2002). 2.3. Data analysis We used a MANOVA with between-subject factor GROUP (AD or control) and within-subject factor SIDE (left or right arm) for thresholds and tolerances for thermal and electrical pain as an overall test to compare AD with matched control subjects and to test for interdependencies of the parameters assessed. Followup univariate mixed two-way ANOVAs were computed for thresholds and tolerances for thermal and electrical pain with factors GROUP and SIDE. For further examination of differences between patients and controls planned post-hoc t tests were performed, results are displayed in Fig. 1. In order to assess interactions between the level of depression and pain perception, HAM-D scores were correlated with all pain parameters for each side.
Fig. 1. Results of pain testing for patients suffering from adjustment disorder with depressed mood (patients) compared to controls: thermal pain thresholds (a) and thermal pain tolerances (b) are significantly increased on the right arm. Electrical pain thresholds (c) were similar in patients and controls whereas electrical pain tolerances (d) were significantly increased on the right arm. No significant differences were observed on the left arm for any electrical pain parameter. Levels of significance of t tests are indicated as follows: *p < 0.05; **p < 0.01. Data presented as mean ± standard error of mean.
were significant for both TPT [F(1, 28) = 6.4; p = 0.01] and TPTO [F(1, 28) = 8.4; p = 0.007]. Planned posthoc t tests revealed a significant higher thermal pain threshold and tolerance for AD patients on the right hand side, whereas TPT and TPTO on the left hand side showed no significant difference as displayed in Fig. 1. 3.3. Electrical pain threshold and tolerance
The MANOVA revealed a significant overall effect for the factor GROUP (WilkÕs Lambda = 0.69; F(4, 25) = 2.78; p = 0.04) when both the AD group and controls were compared. A trend for the multivariate GROUP · SIDE interaction was observed with WilkÕs Lambda = 0.73; F(4, 25) = 2.3; p = 0.08.
Follow-up univariate ANOVAs for the AD group versus controls showed significant main effects of GROUP for EPTO [F(1, 28) = 4.5; p = 0.04] and a trend for EPT [F(1, 28) = 3.7; p = 0.06]. There were no significant GROUP · SIDE interactions. Planned post-hoc t tests revealed a significantly higher electrical pain tolerance for AD patients on the right-hand side, whereas EPT and EPTO on the left hand side showed no significant differences as displayed in Fig. 1. Again, there was a trend for higher EPT in AD patients on the right side (p = 0.06).
3.2. Thermal pain threshold and tolerance
3.4. Correlation of pain parameters with disease severity
Follow-up univariate ANOVAs for AD patients and controls revealed significant main effects of GROUP for thermal pain threshold (TPT) [F(1, 28) = 4.2; p = 0.04] and for thermal pain threshold and tolerance (TPTO) [F(1, 28) = 5.1; p = 0.03]. GROUP · SIDE interactions
The correlation analyses revealed that TPT on the right hand showed a significant positive relationship (r = 0.57, p = 0.02) with HAM-D score, indicating that severely depressed patients had a higher thermal pain threshold on the right side. All other pain parameters
3. Results 3.1. Multivariate statistics
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did not correlate with HAMD scores. A possible indication for a correlation of EPTO on the right-hand side (r = 0.4, p = 0.1) with HAMD scores was observed.
4. Discussion This is the first study on pain perception for experimentally induced pain in patients suffering from adjustment disorder (AD). Interestingly, pain thresholds and tolerances for thermal and electrical pain were significantly increased in the right arm. The patients studied suffered from an acute AD (depressive subtype) subsequent to a recent interpersonal crisis. Therefore the reduced sensitivity to pain might be comparable to the previously described hypoalgesia in major depressive disorder (MDD) (Lautenbacher et al., 1999; Ba¨r et al., 2003, 2005; Dickens et al., 2003). However, in contrast to most depressive patients, our patients were acutely ill for a short period of time only. The moderately depressed patients included in our study scored 15.7 ± 3.6 on the Hamilton depression rating scale (HAM-D), which is markedly increased in comparison to matched controls (
