Biomedical subjects
Publications and source records attributed to Per Hansson.
The paper addresses issues related to the clinical relevance of currently employed animal models of neuropathic pain and our inability to translate clinical symptoms and signs into pathophysiological mechanisms. A mechanism-based classification of pain is therefore currently not feasible. Suggestions on how to facilitate progress within this area are put forward.
Several functional imaging studies of pain, using a number of different experimental paradigms and a variety of reference states, have failed to detect activations in the somatosensory cortices, while other imaging studies of pain have reported significant activations in these regions. The role of the somatosensory areas in pain processing has therefore been debated. In the present study the left hand was immersed in painfully cold water (standard cold pressor test) and in nonpainfully cold water during 2 min, and PET-scans were obtained either during the first or the second minute of stimulation. We observed no significant increase of activity in the somatosensory regions when the painful conditions were directly compared with the control conditions. In order to better understand the role of the primary somatosensory cortex (S1) in pain processing we used a regression analysis to study the relation between a ROI (region of interest) in the somatotopic S1-area for the stimulated hand and other regions known to be involved in pain processing. We hypothesized that although no increased activity was observed in the S1 during pain, this region would change its covariation pattern during noxious input as compared to the control stimulation if it is involved in or affected by the processing of pain. In the nonpainful cold conditions widespread regions of the ipsilateral and contralateral somatosensory cortex showed a positive covariation with the activity in the S1-ROI. However, during the first and second minute of pain this regression was significantly attenuated. During the second minute of painful stimulation there was a significant positive covariation between the activity in the S1-ROI and the other regions that are known to be involved in pain processing. Importantly, this relation was significantly stronger for the insula and the orbitofrontal cortex bilaterally when compared to the nonpainful state. The results indicate that the S1-cortex may be engaged in or affected by the processing of pain although no differential activity is observed when pain is compared with the reference condition.
The aim of this study was to investigate the influence of experimental pain intensity in the local and referred pain area on somatosensory perception thresholds in the area of referred pain. Pain was induced by intramuscular electrical stimulation of the left infraspinatus muscle in 12 healthy individuals. The stimulation corresponded to the local pain threshold ("mild local pain"), the referred pain threshold ("mild referred pain"), and a pain intensity corresponding to 2 on a 10-point category scale in the referred pain area ("moderate referred pain"). Quantitative sensory testing was performed to assess perception thresholds in the referred pain area and the homologous contralateral area before and during stimulation. Perception thresholds to light touch (LTTs), pressure pain (PPTs), and to innocuous as well as noxious warmth and cold were assessed. During stimulation the LTTs increased in the referred pain area compared to baseline, uninfluenced by pain intensity. Perception thresholds to innocuous cold and warmth increased bilaterally during the stimulation, without relation to pain intensity. Heat pain thresholds were not affected. Compared to baseline, PPTs increased bilaterally during stimulation corresponding to "mild local pain" and "mild referred pain", respectively, and a further increase was seen during "moderate referred pain". The decreased sensitivity to innocuous cold, warmth, and pressure pain was bilateral, indicating activation of endogenous net inhibitory mechanisms interacting bilaterally. We found no influence of pain intensity on somatosensory thresholds restricted to the referred pain area and light touch was the only affected modality in the referred pain area only.
In patients with localized musculoskeletal pain, spread of pain and tenderness outside the primarily painful area and sometimes even generalization of pain have been reported, the latter possibly indicating a dysfunction of endogenous pain modulatory systems. The purpose of the study was to use patients with long-term trapezius myalgia as a model to investigate the possible influence of a localized muscle pain on somatosensory processing in a remote pain-free area and the effect of heterotopic noxious conditioning stimulation (HNCS) on 'diffuse noxious inhibitory controls' (DNIC) related mechanisms. Altered somatosensory processing may indicate subclinical derangement of endogenous modulatory systems. Ten patients with long-term (> or = 1 year) trapezius myalgia and 10 age- and sex-matched healthy controls participated. Pressure pain sensitivity, low threshold mechanoreceptive function and thermal sensitivity, including thermal pain, were assessed at the right thigh before, during and following HNCS. Pain was induced in the forearm by the tourniquet test. At rest allodynia to pressure was found at the thigh in conjunction with hypoaesthesia to cold (p<0.03 and p<0.01 respectively), in patients compared with controls. During HNCS, the sensitivity to pressure pain and suprathreshold heat pain decreased in patients and controls alike (p<0.02 and p<0.04 respectively) and returned to baseline following HNCS. In conclusion, in a remote non-painful area allodynia to pressure and hypoaesthesia to cold were found in conjunction with preserved function of DNIC-related mechanisms. Whether altered central somatosensory processing at rest may indicate a predisposition for further spread of pain is at present unclear.
The purpose was to investigate the influence of ongoing pain from an inflammatory nociceptive pain with two different disease durations on somatosensory functions and the effect of heterotopic noxious conditioning stimulation (HNCS) on 'diffuse noxious inhibitory controls' (DNIC) related mechanisms. Eleven patients with rheumatoid arthritis of a short duration (<1 year) (RA1), and 10 patients with rheumatoid arthritis of longer duration (>5 years) (RA5) as well as 21 age- and sex-matched healthy controls participated. Pressure pain sensitivity, low threshold mechanoreceptive function and thermal sensitivity, including thermal pain, were assessed over a painful and inflamed joint as well as in a pain-free area, i.e. the right thigh before HNCS (cold-pressor test) and repeated at the thigh only during and following HNCS. In RA1 and RA5 allodynia to pressure was seen over the joint (p<0.02 and p<0.001 respectively) in conjunction with hypoaesthesia to light touch (p<0.02) and hyperaesthesia to innocuous cold (p<0.05) in RA5. At the thigh, allodynia to pressure was found in RA5 (p<0.002). During HNCS, the sensitivity to pressure pain decreased in patients and controls alike (p<0.001). In conclusion, over an inflamed joint allodynia to pressure was found in both RA groups, with additional sensory abnormalities in RA5. In a non-painful area, allodynia to pressure was found in RA5, suggesting altered central processing of somatosensory functions in RA5 patients. The response to HNCS was similar in both RA groups and controls, indicating preserved function of DNIC-related mechanisms.
Neuropathic pain is part of the neurological disease spectrum and may be an expression of severe medical pathology. Painful neuropathies have multiple disguises and may to a certain extent be mimicked by non-neurological pain conditions. Painful neuropathic conditions express themselves with spontaneous and/or abnormal stimulus-evoked pain. The diagnosis of peripheral or central neuropathic pain should be made only when the history and signs are indicative of neuropathy in conjunction with neuroanatomically correlated pain distribution and sensory abnormalities within the area of pain. A future mechanism-based classification of pain has recently been suggested to facilitate the development of mechanism-tailored treatment strategies. This is a sound approach and should be pursued. It is mandatory, however, to retain the traditional organ-based diagnostic workup, which should precede further in-depth characterization of specific pain mechanisms. Extensive preparatory work is needed on how to link certain symptoms and signs to specific mechanisms, as elucidated from animal studies, before we can introduce mechanism-coupled treatment strategies.
Reconstruction of the nipple-areola complex is the final procedure of a breast reconstruction. The method of choice in our department for nipple reconstruction is nipple-sharing and tattooing of the areola. Some patients are reluctant to use a part of the healthy nipple, as it is not fully known how the sensibility in the remaining donor nipple is affected by surgery. Twenty patients admitted to the hospital for nipple-sharing were invited to participate in the study. The tactile perception threshold of the donor nipple was assessed using von Frey monofilaments preoperatively, and 1, 6, and 12 months postoperatively. The patients' subjective impressions one year postoperatively were also evaluated. The donor nipple had regained sensibility to touch six months after nipple-sharing. All patients reported that the nipple felt the same as before surgery and could become erect. We therefore recommend the nipple-sharing technique for completion of a breast reconstruction.
This study aimed at evaluating the influence of submaximal isometric contraction on pressure pain thresholds (PPTs) in 14 fibromyalgia (FM) patients and 14 healthy volunteers, before and after skin hypoesthesia. PPTs were determined with pressure algometry over m. quadriceps femoris before, during and following an isometric contraction. Maximum voluntary contraction (MVC) was assessed using a computerized dynamometer. A contraction of 22% MVC on average was held until exhaustion (max. 5 min) and PPTs were assessed every 30 sec. A local anesthetic cream and a control cream were applied following a double-blind design and PPTs were reassessed. In healthy volunteers PPTs increased during contraction (P < 0.001), then decreased after the end of contraction (P < 0.001) but remained above precontraction values during the 5 min of post-contraction assessments (P < 0.001). In FM patients PPTs decreased in the middle of the contraction period (P < 0.05) and remained below precontraction levels during the rest of the contraction period (P < 0.05) and during the 5 min of post-contraction assessment (immediately post-contraction NS; 2.5 min post-contraction P < 0.01; 5 min post-contraction P < 0.05). The normalized PPTs were significantly lower in patients than in controls during contraction (start P < 0.01; middle P < 0.001; end P < 0.001) and at all times during post-contraction assessments (P < 0.001). Anesthetic cream raised PPTs at rest in controls (P < 0.01) but not in FM patients, and did not influence contraction or post-contraction PPTs in either group. Therefore, the increased pressure pain sensibility in FM patients is more pronounced deep to the skin. The observed decrease of PPTs during isometric contraction in FM patients could be due to sensitization of mechanonociceptors caused by muscle ischemia and/or dysfunction in pain modulation during muscle contraction.
Adenosine, an endogenous antinociceptive compound acting in the central nervous system, was infused intravenously (50-70 micrograms/kg/min) to 2 patients with peripheral neuropathic pain. In 1 subject, spontaneous pain was alleviated, and tactile allodynia was essentially relieved during 40 min of infusion. Allodynia to warmth and touch were abolished in the other subject. In addition, hyperalgesia to pinprick was markedly attenuated as was pressure-induced allodynia. The reported effects lasted for hours after termination of the infusion. Our preliminary encouraging data call for further controlled studies of the potentially relieving effect of adenosine in painful neuropathic conditions.
This study was undertaken to explore whether the neural substrates demonstrated in brain imaging studies on experimentally induced pain are involved in the perception of chronic neuropathic pain. We investigated the cerebral representation of chronic lateralised ongoing pain in patients with painful mononeuropathy (PMN, i.e., pain in the distribution of a nerve, neuralgia) with positron emission tomography (PET), using regional cerebral blood flow (rCBF) as an index for neuronal activity. Eight patients (29-53 years) with PMN in the lower extremity (4 in the right, 4 in the left) were recruited. Paired comparisons of rCBF were made between the patient's habitual pain (HP) state and the pain alleviated (PA) state following a successful regional nerve block (RNB) with lidocaine. The ongoing neuropathic pain resulted in activation of bilateral anterior insula, posterior parietal, lateral inferior prefrontal, and posterior cingulate cortices as well as the posterior sector of the right anterior cingulate cortex (ACC), Brodmann area (BA) 24, regardless of the side of PMN. In addition, a reduction in rCBF was noted in the contralateral posterior thalamus. No significant change of rCBF was detected in the somatosensory areas, i.e., SI and SII. The cerebral activation pattern, while addressing the differences between the HP and PA states, emphasises the affective-motivational dimension in chronic ongoing neuropathic pain. The striking preferential activation of the right ACC (BA 24), regardless of the side of the PMN, not only confirms that the ACC participates in the sensorial/affectional aspect of the pain experience but also suggests a possible right hemispheric lateralisation of the ACC for affective processing in chronic ongoing neuropathic pain. Our data suggests that the brain employs different central mechanisms for chronic neuropathic pain and experimentally induced acute pain, respectively.
This study was aimed at comparing pressure pain sensibility in different tissues in fibromyalgia patients. Pressure pain thresholds (PPTs) were assessed in 16 fibromyalgia (FM) patients bilaterally at the bony part of epicondylus lateralis humeri, at the belly of m. extensor carpi ulnaris and at m. brachioradialis where the radial nerve branches pass underneath. Following a double-blind design, either a local anesthetic cream (EMLA) or a control cream was applied to the skin and PPTs were reassessed. The site with underlying nerve had a lower PPT than the bony site (P < 0.001) and the 'pure' muscle site (P < 0.001), respectively. These relations remained unaltered by skin hypoesthesia. The PPTs over the bony and the 'pure' muscle sites did not differ. Application of EMLA, compared to control cream, did not change PPTs over any area examined. The results demonstrated that pressure-induced pain sensibility in FM patients is not most pronounced in muscle tissue and does not depend on increased skin sensibility.
Aiming at optimizing serotonin levels in endogenous pain-modulating systems, L-tryptophan supplementation pre- and postoperatively (2 g/day for 7 days) did not affect pain development or analgesic consumption after third molar surgery. Biological effects related to an increase in mood were observed, however, indicating transport of L-tryptophan to the central nervous system. The findings are discussed in relation to earlier reports on favorable effects of L-tryptophan on experimental pain in healthy subjects and in chronic pain patients.
The present paper describes the pain reducing effect of high and low frequency transcutaneous electrical nerve stimulation (TENS) and 100 Hz mechanical vibratory stimulation as compared to placebo stimulation of the HoKu point in 50 patients suffering acute oro-facial pain. Ten of the 30 patients receiving actual stimulation reported pain reduction during treatment. In the placebo group of 20 patients, 4 of the subjects experienced pain relief during the trial. The findings in the present study showed that extrasegmental superficial stimulation of the HoKu point alters pain intensity in the patients studied to only a minor degree. The number of patients reporting pain alleviation and the magnitude of pain reduction in the groups receiving actual stimulation was comparable to that observed in earlier studies using intrasegmental placebo stimulation.
In the present paper it is demonstrated that transcutaneous electrical nerve stimulation (TENS) and vibratory stimulation can reduce pathological pain but give insufficient pain reduction to allow dental and oral surgery. Thirty-seven patients were assigned to one of 4 groups receiving either TENS of high (100 Hz) or low (2 Hz) frequency, vibration at 100 Hz or placebo stimulation. Pain intensity was continuously assessed. A crude assessment of pinprick threshold, paraesthesia and anaesthesia was made prior to the clinical treatment. After 30 min of afferent stimulation the surgical treatment was started, aiming at pulp surgery, abscess incision or tooth extraction. However, all patients experienced intolerable pain at these attempts although about half of the patients experienced relief of their pathological pain, increase in pinprick threshold, paraesthesia as well as anaesthesia during the stimulation period. All patients were thus given conventional local anaesthesia and were all painlessly treated.
The present paper describes the effect of vibratory stimulation on pain of dental origin in 36 patients. The patients were from a clinic for dental surgery and all had suffered pain from pulpal inflammation, apical periodontitis or postoperative pain following extraction of an impacted wisdom tooth for more than 2 days. Vibration at 100 Hz was applied to various points in the facial region or the skull. All the patients except three experienced an effective reduction of the intensity of the pain. In the patients who experienced pain reduction there was usually a best point at which vibration had a greater pain alleviating effect than at other points. At some points the stimulation added to the pain. In 16 patients the stimulation caused a reduction in pain intensity of 75--100%; out of these 12 patients reported a complete relief of pain.
In 1996, the Endocrinology Group in EQUALIS, in collaboration with The Thyroid Unit at The Section of Endocrinology at Sahlgrenska University Hospital, introduced a "patient-related" quality assurance program. Serum samples from patients with established or suspected thyroid disorder and/or results from thyroid-related biochemical measurements which were at variance with the clinical presentation, were analyzed by the participants of an external quality assurance program in endocrinology. The results from this program were informative as regards capacity, in the individual laboratories, for the evaluation of analytical and/or biological factors causing unexpected results from the measurement of thyroid-related serum components. We now present four clinical cases, which had offered diagnostic problems. EQUALIS, in collaboration with the participants of the external quality assurance program in endocrinology and on the basis of experiences from this program, now offers a diagnostic service for clinical chemistry laboratories and physicians when they are confronted with unexpected results from the immunochemical measurement of analytes included in the program.