Volume 2, Issue 4

Background and aims Burning mouth syndrome (BMS) and atypical facial pain (AFP) are often persistent idiopathic pain conditions that mainly affect middle-aged and elderly women. They have both been associated with various psychiatric disorders. This study examined current and lifetime prevalence of psychiatric axis I (symptom-based) and II (personality) disorders in patients with chronic idiopathic orofacial pain, and investigated the temporal relationship of psychiatric disorders and the onset of orofacial pain. Method Forty patients with BMS and 23 patients with AFP were recruited from Turku university hospital clinics. Mean age of the patients was 62.3 years (range 35–84) and 90% were female. BMS and AFP diagnoses were based on thorough clinical evaluation, and all patients had undergone clinical neurophysiological investigations including blink reflex and thermal quantitative tests. Current and lifetime DSM-IV diagnoses of axis I and II disorders were made on clinical basis with the aid of SCID-I and II-interviews. The detected prevalence rates and their 95% confidence intervals based on binomial distribution were compared to three previous large population-based studies. Results Of the 63 patients, 26 (41.3%) had had an axis I disorder that preceded the onset of orofacial pain, and 33 (52.4%) had had a lifetime axis I disorder. Rate of current axis I disorders was 36.5%, indicating that only about 16% of lifetime disorders had remitted, and they tended to run chronic course. The most common lifetime axis I disorders were major depression (30.2%), social phobia (15.9%), specific phobia (11.1%), and panic disorder (7.9%). Twelve patients (19.0%) had at least one cluster C personality disorder already before the emergence of orofacial pain. Patients with cluster C personality disorders are characterized as fearful and neurotic. None of the patients had cluster A (characterized as odd and eccentric) or B (characterized as dramatic, emotional or erratic) personality disorders. The most common personality disorders were obsessive–compulsive personality (14.3%), dependent personality (4.8%), and avoidant personality (3.2%). The majority of the patients (54%) had also one or more chronic pain conditions other than orofacial pain. In almost all patients (94%) they were already present at the onset of orofacial pain. Conclusions Our results suggest that major depression, persistent social phobia, and neurotic, fearful, and obsessive–compulsive personality characteristics are common in patients with chronic idiopathic orofacial pain. Most psychiatric disorders precede the onset of orofacial pain and they tend to run a chronic course. Implications We propose that the high psychiatric morbidity, and comorbidity to other chronic pain conditions, in chronic idiopathic orofacial pain can be best understood in terms of shared vulnerability to both chronic pain and specific psychiatric disorders, most likely mediated by dysfunctional brain dopamine activity.

Background and purpose Conditioned pain modulation (CPM) is a phenomenon in which pain is inhibited by heterotopic noxious stimulation. It is not known how the experimental condition affects the magnitude of the CPM response and the inter-and intra-individual variations. It is important to get the information of the test–retest reliability and inter–individual variations of CPM to apply CPM as a diagnostic tool or for screening analgesic compounds. This study evaluated (1) the magnitude of CPM, (2) the inter-individual coefficient of variation (inter-CV) and (3) the intra-individual coefficient of variation (intra-CV) to (A) different stimulus modalities to evoke CPM and (B) different assessment sites. Methods Twelve healthy men (age 19–38 years) participated in this study. Cold pressor pain (CPP) (immersing the hand into cold water), tourniquet pain (cuff around the upper arm) and mechanical pressure pain (craniofacial region) were used in randomized order as conditioning stimuli (CS). The test stimulus (TS) was pressure pain applied to the right masseter muscle, left forearm and leg (bilateral tibialis anterior: TA). The responses were pressure pain thresholds (PPT), pressure pain tolerance (PPTol) thresholds and the pain intensity which was assessed on a visual analogue scale (VAS, 0–10 cm) following 1.4 and 1.6 × PPT applied to TA. The TS was applied before, during and 10 min after the CS. The intra-individual CV was estimated between different days. Results CPP induced the most powerful CPM on PPT (66.3 ± 10.0% increase), VAS ratings (41.5 ± 5.3% reduction) and PPTol (32.6±4.6% increase), especially at TA, and resulted in the smallest inter-CV (41.4–60.1%). Independently of the CS, the inter-CV in general showed that the recordings from the orofacial region and the forearm had smaller values than from the leg. The smallest intra-CV value was obtained in pain ratings with CPP (27.0%). Conclusions This study suggests that (1) the CPP evokes the largest CPM, (2) the leg as the assessment site results in the largest CPM responses and (3) the CPP causes the smallest inter- and intra-CV. Implication The present investigation implicates that the CPP is the most efficient conditioning stimulus to induce CPM when assessed by pressure pain thresholds.

Introduction Animal disease models are predictive for signs seen in disease. They may rarely mimic all signs in a specific disease in humans with respect to etiology, cause or development. Several models have been developed for different pain states and the alteration of behavior has been interpreted as a response to external stimulus or expression of pain or discomfort. Considerable attention must be paid not to interpret other effects such as somnolence or motor impairment as a pain response and similarly not to misinterpret the response of analgesics. Neuropathic pain is caused by injury or disease of the somatosensory system. The clinical manifestations of neuropathic pain vary including both stimulus-evoked and non-stimulus evoked (spontaneous) symptoms. By pharmacological intervention, the threshold for allodynia and hyperalgesia in the various pain modalities can be modulated and measured in animals and humans. Animal models have been found most valuable in studies on neuropathic pain and its treatment. Aim of the study With these interpretation problems in mind, the present text aims to describe the most frequently used animal models of neuropathic pain induced by mechanical nerve injury. Methods The technical surgical performance of these models is described as well as pain behavior based on the authors own experience and from a literature survey. Results Nerve injury in the hind limb of rats and mice is frequently used in neuropathic pain models and the different types of lesion may afford difference in the spread and quality of the pain provoked. The most frequently used models are presented, with special focus on the spared nerve injury (SNI) and the spinal nerve ligation/transection (SNL/SNT) models, which are extensively used and validated in rats and mice. Measures of mechanical and thermal hypersensitivity with von Frey filaments and Hargreaves test, respectively, are described and shown in figures. Conclusions A number of animal models have been developed and described for neuropathic pain showing predictive value in parallel for both humans and animals. On the other hand, there are still large knowledge gaps in the pathophysiologic mechanisms for the development, maintenance and progression of the neuropathic pain syndrome Implications Better understanding of pathogenic mechanisms of neuropathic pain in animal models may support the search for new treatment paradigms in patients with complex neuropathic pain conditions

Introduction The pathophysiologic and neurochemical characteristics of neuropathic pain must be considered in the search for new treatment targets. Breakthroughs in the understanding of the structural and biochemical changes in neuropathy have opened up possibilities to explore new treatment paradigms. However, long term sequels from the damage are still difficult to treat. Aim of the study To examine the validity of pharmacological treatments in humans and animals for neuropathic pain. Method An overview from the literature and own experiences of pharmacological treatments employed to interfere in pain behavior in different animal models was performed. Results The treatment principles tested in animal models of neuropathic pain may have predictive validity for treatment of human neuropathies. Opioids, neurotransmitter blockers, drugs interfering with the prostaglandin syntheses as well as voltage gated sodium channel blockers and calcium channel blockers are treatment principles having efficacy and similar potency in humans and in animals. Alternative targets have been identified and have shown promising results in the validated animal models. Modulators of the glutamate system with an increased expression of glutamate re-uptake transporters, inhibition of pain promoters as nitric oxide and prostaglandins need further exploration. Modulation of cytokines and neurotrophins in neuropathic pain implies new targets for study. Further, a combination of different analgesic treatments may as well improve management of neuropathic pain, changing the benefit/risk ratio. Implications Not surprisingly most pharmacologic principles that are tested in animal models of neuropathic pain are also found to be active in humans. Whereas many candidate drugs that were promising in animal models of neuropathic pain turned out not to be effective or too toxic in humans, animal models for neuropathic pain are still the best tools available to learn more about mechanisms of neuropathic pain. Better understanding of pathogenesis is the most hopeful approach to improve treatment of neuropathic pain.

Introduction and aim Pain is a frequent symptom in emergency patients and opioids are commonly used to treat it at emergency departments and at pre-hospital settings. The aim of this systematic review is to examine the efficacy and safety of parenteral opioids used for acute pain in emergency medicine. Method Qualitative review of randomized controlled trials (RCTs) on parenteral opioids for acute pain in adult emergency patients. Main outcome measures were: type and dose of the opioid, analgesic efficacy as compared to either placebo or another opioid and adverse effects. Results Twenty double-blind RCTs with results on 2322 patients were included. Seven studies were placebo controlled. Majority of studies were performed in the emergency department. Only five studies were in prehospital setting. Prehospital studies Four studies were on mainly trauma-related pain, one ischemic chest pain. One study compared two different doses of morphine in mainly trauma pain showing faster analgesia with the larger dose but no difference at 30 min postdrug. Three other studies on the same pain model showed equal analgesic effects with morphine and other opioids. Alfentanil was more effective than morphine in ischemic chest pain. Emergency department studies Pain models used were acute abdominal pain seven, renal colic four, mixed (mainly abdominal pain) three and trauma pain one study. Five studies compared morphine to placebo in acute abdominal pain and in all studies morphine was more effective than placebo. In four out of five studies on acute abdominal pain morphine did not change diagnostic accuracy, clinical or radiological findings. Most commonly used morphine dose in the emergency department was 0.1 mg/kg (five studies). Other opioids showed analgesic effect comparable to morphine. Adverse effects Recording and reporting of adverse effects was very variable. Vital signs were recorded in 15 of the 20 studies (including all prehospital studies). Incidence of adverse effects in the opioid groups was 5–38% of the patients in the prehospital setting and 4–46% of the patients in the emergency department. Nausea or vomiting was reported in 11–25% of the patients given opioids. Study drug was discontinued because of adverse effects five patients (one placebo, two sufentanil, two morphine). Eight studies commented on administration of naloxone for reversal of opioid effects. One patient out of 1266 was given naloxone for drowsiness. Ventilatory depression defined by variable criteria occurred in occurred in 7 out of 756 emergency department patients. Conclusion Evidence for selection of optimal opioid and dose is scarce. Opioids, especially morphine, are effective in relieving acute pain also in emergency medicine patients. Studies so far are small and reporting of adverse effects is very variable. Therefore the safety of different opioids and doses remains to be studied. Also the optimal titration regimens need to be evaluated in future studies. The prevention and treatment of opioid-induced nausea and vomiting is an important clinical consideration that requires further clinical and scientific attention in this patient group.