Volume 2, Issue 3

During the last decades there has been a tremendous development of non-invasive methods for assessment of brain activity following visceral pain. Improved methods for neurophysiological and brain imaging techniques have vastly increased our understanding of the central processing of gastrointestinal sensation and pain in both healthy volunteers as well as in patients suffering from gastrointestinal disorders. The techniques used are functional magnetic resonance imaging (fMRI), positron emission tomography (PET), electroencephalography (EEG)/evoked brain potentials (EPs), magnetoencephalography (MEG), single photon emission computed tomography (SPECT), and the multimodal combinations of these techniques. The use of these techniques has brought new insight into the complex brain processes underlying pain perception, including a number of subcortical and cortical regions, and paved new ways in our understanding of acute and chronic pain. The pathways are dynamic with a delicate balance between facilitatory and inhibitory pain mechanisms, and with modulation of the response to internal or external stressors with a high degree of plasticity. Hence, the ultimate goal in imaging of pain is to follow the stimulus response throughout the neuraxis. Brain activity measured by fMRI is based on subtracting regional changes in blood oxygenation during a resting condition from the signal during a stimulus condition, and has high spatial resolution but low temporal resolution. SPECT and PET are nuclear imaging techniques where radiolabeled molecules are injected with visualization of the distribution, density and activity of receptors in the brain allowing not only assessment of brain activity but also study of receptor sites. EEG is based on assessment of electrical activity in the brain, and recordings of the resting EEG and evoked potentials following an external stimulus are used to study normal visceral pain processing, alterations of pain processing in different patient groups and the effect of pharmacological intervention. EEG has high temporal resolution, but relative poor spatial resolution, which however to some extent can be overcome by applying inverse modelling algorithms and signal decomposition procedures. MEG is based on recording the magnetic fields produced by electrical currents in the brain, has high spatial resolution and is especially suitable for the study cortical activation. The treatment of chronic abdominal pain is often ineffective and dissapointing, which leads to search for optimized treatment achieved on the basis of a better understanding of underlying pain mechanisms. Application of the recent improvements in neuroimaging on the visceral pain system may likely in near future contribute substantially to our understanding of the functional and structural pathophysiology underlying chronic visceral pain disorders, and pave the road for optimized individual and mechanism based treatments. The purpose of this review is to give a state-of-the-art overview of these methods, with focus on EEG, and especially the advantages and limitations of the single methods in clinical gastrointestinal pain esearch including examples from relevant studies.

Background and purpose : A noxious stimulus does not necessarily cause pain. Nociceptive signals arising from a noxious stimulus are subject to modulation via endogenous inhibitory and facilitatory mechanisms as they travel from the periphery to the dorsal horn or brainstem and on to higher brain sites. Research on the neural structures underlying endogenous pain modulation has largely been restricted to animal research due to the invasiveness of such studies (e.g., spinal cord transection, brain lesioning, brain site stimulation). Neuroimaging techniques (e.g., magnetoencephalography (MEG), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI)) provide non-invasive means to study neural structures in humans. The aim is to provide a narrative review of neuroimaging studies related to human pain control mechanisms. Methods : The approach taken is to summarise specific pain modulation mechanisms within the somatosensory (diffuse noxious inhibitory controls, acupuncture, movement), affective (depression, anxiety, catastrophizing, stress) and cognitive (anticipation/placebo, attention/distraction, hypnosis)domains with emphasis on the contribution of neuroimaging studies. Results and conclusions : Findings from imaging studies are complex reflecting activation or deactivation in numerous brain areas. Despite this, neuroimaging techniques have clarified supraspinal sites involved in a number of pain control mechanisms. The periaqueductal grey (PAG) is one area that has consistently been shown to be activated across the majority of pain mechanisms. Activity in the rostral ventromedial medulla known to relay descending modulation from the PAG, has also been observed both during acupuncture analgesia and anxiety-induced hyperalgesia. Other brain areas that appear to be involved in a number of mechanisms are the anterior cingulate cortex, prefrontal cortex, orbitofrontal cortex and nucleus accumbens, but their exact role is less clear. Implications : Neuroimaging studies have provided essential information about the pain modulatory pathways under normal conditions, but much is still to be determined. Understanding the mechanisms of pain control is important for understanding the mechanisms that contribute to failed pain control in chronic pain. Applying fMRI outside the brain, such as in the trigeminal nucleus caudalis of the spinotrigeminal pathway and in the dorsal horn of the spinal cord, and coupling brain activity with activity at these sites may help improve our understanding of the function of brain sites and shed light on functional connectivity in the pain pathway. © 2011 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Historic background and development of our somatocognitive approach Mensendieck physiotherapy of the Oslo School is a tradition of physiotherapy founded by the American physician Bess Mensendieck, a contemporary and fellow student of Sigmund Freud at the Paris School of Neurology. It builds on the principles of functional anatomy and the theories of motor learning. We have further developed the theory and practice from this physiotherapy tradition, challenged by the enormous load of patients with longstanding, incapacitating pain on western health care systems, by seeking to incorporate inspirational ideas from body oriented dynamic psychotherapy and cognitive psychotherapy. We developed somatocognitive therapy as a hybrid of physiotherapy and cognitive psychotherapy by focusing on the present cognitive content of the mind of the patient, contrary to a focus on analysis of the subconscious and interpretation of dreams, and acknowledging the important role of the body in pain-eliciting defense mechanisms against mental stress and negative emotions. The core of this somatocognitive therapy (1) To promote awareness of own body, (2) graded task assignment related to the motor patterns utilized in daily activities, (3) combined with an empathic attitude built on dialogue and mutual understanding, and emotional containment and support. The goal is for the patient to develop coping strategies and mastery of own life. In addition, (4) manual release of tensed muscles and applied relaxation techniques are important. Methods and results of an illustrative study One area in particular need of development and research is sexual pain disorders. We have applied this somatocognitive therapy in a randomized, controlled intervention study of women with chronic pelvic pain (CPP).Wesummarize methods and results of this study. Methods 40 patients with CPP were included in a randomized, controlled intervention study. The patients were randomized into (1) a control group, receiving treatment as usual (Standard Gynecological Treatment, STGT) and (2) a group receiving STGT + Mensendieck Somatocognitive Therapy (MSCT). The patients were assessed by means of Visual Analogue Scale of Pain (VASP), Standardized Mensendieck Test (SMT) for analysis of motor patterns (posture, movement, gait, sitting posture and respiration), and General Health Questionnaire (GHQ-30) assessing psychological distress, at baseline (inclusion into study), after three months of out-patient therapy and at 1 year follow-up. Results: The women averaged 31 years, pain duration 6.1 years, average number of previous surgical procedures 1.8 per women. In the STGT group, no significant change was found, neither in pain scores, motor patterns or psychological distress during the observation period. In the group receiving STGT + MSCT, significant reduction in pain score and improvement in motor function were found at the end of therapy, and the significant improvement continued through the follow-up (64% reduction of pain scores, and 80% increase in the average score for respiration, as an example of motor pattern improvement). GHQ scores were significantly improved for anxiety and coping ( p < 0.01). Conclusions Somatocognitive therapy is anewapproach that appears to be very promising in the management of chronic gynecological pain. Short-term out-patient treatment significantly reduces pain scores and improves motor function. Implications Chronic pelvic pain in women is a major health care problem with no specific therapies and poor prognosis. A novel, somatocognitive approach has documented positive effects. It is now studied by other clinical researchers in order to reinforce its evidence base.

Glutamate is the major excitatory amino acid in the mammalian CNS and is involved in transmission of pain together with processes for cognition, memory and learning. In order to terminate glutamatergic neurotransmission and avoid excitotoxic damage, a balanced glutamate homeostasis is of critical importance. The level of glutamate in the synaptic cleft is regulated through the action of five subtypes of excitatory amino acid transporters (EAAT1-5). Ceftriaxone, a β-lactam, induces EAAT-2 and has proven effect for the treatment of neuropathic pain. This pilot study investigated the effects of ceftriaxone upon acute and inflammatory pain and additionally, the analgesic effect of ceftriaxone after introduction of neuropathic pain. Methods Rats were tested before, during and after treatment of ceftriaxone for changes in response to both mechanical and thermal stimuli, using calibrated von Frey filaments and Hargreaves instrument, respectively. Inflammatory responses were investigated by assessing the response to intra-plantar injections of formalin; lastly, neuropathic pain was introduced using the spinal nerve ligation (SNL) model after which changes in both mechanical and thermal responses were again investigated. Results A significant increase in mechanical withdrawal threshold was observed following acute pain inducement in ceftriaxone treated rats. A marked increase in thermal withdrawal latency was also observed. In response to intra plantar administered formalin, ceftriaxone delayed the intensity of nocifensive behaviours. Applying the SNL model of neuropathic pain on naive rats created significant mechanical allodynia, but only a negligibly different response to thermal stimulation. After treatment with ceftriaxone the treated rats developed a hypoalgesic response to thermal stimulation, whilst the response to mechanical pain was insignificant. Conclusion In conclusion, ceftriaxone clearly interfered in the transmission of noxious signalling and proved in this study to have an effect upon acute thermal and mechanical pain thresholds as well as pathologic pain conditions. The present results are a piece in the large puzzle where administration route, dosage and pain models must be thoroughly investigated before a study can be planned for a proof of concept in different clinical pain states. Implications The current study demonstrates that ceftriaxone has a mitigating effect upon many pain modalities including acute and inflammatory, and that these modalities should be included in future studies characterising the anti-nociceptive effect of beta-lactams such as ceftriaxone. The fact that β-lactams also has antibiotic properties implies that similar chemical structures could be identified with the positive effect upon expression levels of EAAT2, but lacking the antibiotic side effect.

Background and purpose Spinal cord injury (SCI) has detrimental consequences that include chronic neuropathic pain, which is seen in 40-50% of patients, and symptoms of anxiety and depression, which affect 13-45% of SCI patients. The coexistence of pain, anxiety, and depression is known from other neuropathic pain conditions, but the relationship between these symptoms is not clear and has not been investigated in a preclinical model of SCI so far. The aim of this study was to investigate anxiety-like behavior and at-level mechanical hypersensitivity following experimental spinal cord contusion (SCC) in female Sprague-Dawley rats, and the effects of analgesic and anxiolytic drugs. Methods Mechanical sensitivity and elevated plus maze (EPM) behavior were measured pre- and postinjury in SCC and sham animals. Pregabalin 30 mg/kg, morphine 3 mg/kg, midazolam 0.5 mg/kg, and 0.9% NaCl were evaluated in a randomly allocated, blinded balanced design. Results SCC animals developed persistent at-level mechanical hypersensitivity and decreased open arm activity in the EPM, which indicates an anxiety-like state. Pregabalin, a dual-acting analgesic and anxiolytic drug reduced both hypersensitivity and anxiety-like behavior, while the analgesic drug morphine only reduced hypersensitivity. The anxiolytic drug midazolam in the dose used had no effect on either parameter. Conclusions SCC animals developed long lasting coexisting at-level mechanical hypersensitivity and anxiety-like behavior, but there was no evidence to support a causal relationship between pain and anxiety following SCI. Implications The findings that at-level mechanical hypersensitivity and anxiety-like behavior develops concomitantly in the spinal cord contusion models and that both symptoms is persistent provide basis for further investigation of the mechanisms and connection behind these two clinically relevant symptoms after injury to the central nervous system.

Objective Earlier epidemiological studies have shown that headaches are frequent among adolescents, especially girls. In particular, recurrent primary headache disorders such as migraine and tension-type headaches are common complaints in this age group. Headaches are increasingly being recognized as a significant health problem in adolescents and can lead to significant disabilities by affecting their lives, their school performance and their social lives. The aim of this study was to compare the prevalence of primary headaches among adolescents aged 16-20 years in Norway in two periods. Very few replicate studies have re-evaluated the prevalence of primary headaches in this age range and it is uncertain whether the prevalence is increasing. Methods Two cross-sectional, population-based studies were conducted in Norway from 1995 to 1997 (Young-HUNT 1) and from 1999 to 2001 (Young-HUNT 2). In Young-HUNT 1, 2594 adolescents in 2nd and 3rd grade in upper secondary school (aged 16-20 years) completed a comprehensive questionnaire including one question regarding headache during the last 12 months. In addition, 1730 of the students were interviewed about their headache complaints. In Young-HUNT 2, 2373 adolescents aged 16-20 years completed the same questionnaire and 1655 were interviewed in the same way as the earlier survey. The interviews were performed by trained nurses, and respondents were asked if they had experienced recurrent headache during the last year. If so, the headache was classified as migraine (MI), tensiontype headache (TTH) or non-classifiable headache (NCH). Headache frequency during the past year was recorded according to the following categories: Less than 1 day per month (less than monthly), 1-3 days per month (monthly), 1-5 days per week (weekly), or more than 5 days per week (daily). Results The participation rate was 88% in Young-HUNT 1 and 81% in Young-HUNT 2. The overall prevalence of having had headaches during the last 12 months did not change significantly (79.4% versus 77.5%; OR: 0.89, 95%CI: 0.79-1.02, p = 0.09), whereas the prevalence of recurrent headaches increased from 30.3% in Young-HUNT 1 to 35.4% in Young-HUNT 2 (OR: 1.26, 95%CI: 1.09-1.46, p = 0.002). The prevalence of tension-type headache changed significantly from 19.0% to 21.9% (OR: 1.20, 95%CI: 1.02-1.42, p = 0.03). Also the prevalence of migraine tended to increase (7.5% versus 8.7%, OR: 1.18, 95%CI: 0.92-1.52, p = 0.18). The overall frequency of recurrent headache changed towards more monthly and less weekly headache. Conclusions This is the first large-scale population-based study among adolescents in Norway assessing changes in the prevalence of primary headaches over a four-year period of time. The overall prevalence of recurrent headaches increased significantly from Young-HUNT 1 to Young-HUNT 2. An increase was seen in all types of recurrent headaches and was significant for tension-type headache. Implications Earlier follow-up studies have examined changes in prevalence of recurrent headaches in young age, but the results are diverging. Our findings support the impression that the prevalence of recurrent headache among adolescents is increasing, and underlines the need for prospective designed studies with emphasis on prognosis and etiological factors.