European Academy of Neurology guideline on trigeminal neuralgia.

BACKGROUND AND PURPOSE: Trigeminal neuralgia (TN) is an extremely painful condition which can be difficult to diagnose and treat. In Europe, TN patients are managed by many different specialities. Therefore, there is a great need for comprehensive European guidelines for the management of TN. The European Academy of Neurology asked an expert panel to develop recommendations for a series of questions that are essential for daily clinical management of patients with TN. METHODS: A systematic review of the literature was performed and recommendations was developed based on GRADE, where feasible; if not, a good practice statement was given. RESULTS: The use of the most recent classification system is recommended, which diagnoses TN as primary TN, either classical or idiopathic depending on the degree of neurovascular contact, or as secondary TN caused by pathology other than neurovascular contact. Magnetic resonance imaging (MRI), using a combination of three high-resolution sequences, should be performed as part of the work-up in TN patients, because no clinical characteristics can exclude secondary TN. If MRI is not possible, trigeminal reflexes can be used. Neurovascular contact plays an important role in primary TN, but demonstration of a neurovascular contact should not be used to confirm the diagnosis of TN. Rather, it may help to decide if and when a patient should be referred for microvascular decompression. In acute exacerbations of pain, intravenous infusion of fosphenytoin or lidocaine can be used. For long-term treatment, carbamazepine or oxcarbazepine are recommended as drugs of first choice. Lamotrigine, gabapentin, botulinum toxin type A, pregabalin, baclofen and phenytoin may be used either alone or as add-on therapy. It is recommended that patients should be offered surgery if pain is not sufficiently controlled medically or if medical treatment is poorly tolerated. Microvascular decompression is recommended as first-line surgery in patients with classical TN. No recommendation can be given for choice between any neuroablative treatments or between them and microvascular decompression in patients with idiopathic TN. Neuroablative treatments should be the preferred choice if MRI does not demonstrate any neurovascular contact. Treatment for patients with secondary TN should in general follow the same principles as for primary TN. In addition to medical and surgical management, it is recommended that patients are offered psychological and nursing support. CONCLUSIONS: Compared with previous TN guidelines, there are important changes regarding diagnosis and imaging. These allow better characterization of patients and help in decision making regarding the planning of medical and surgical management. Recommendations on pharmacological and surgical management have been updated. There is a great need for future research on all aspects of TN, including pathophysiology and management.

Does conditioned pain modulation predict the magnitude of placebo effects in patients with neuropathic pain?

BACKGROUND: Conditioned pain modulation (CPM) is a validated measure of the function of endogenous pain inhibitory pathways. Placebo effects reflect top-down inhibitory modulation of pain. CPM and placebo effects are both influenced by expectations, albeit to varying degrees, and are related to neurotransmitter systems such as the endogenous opioid system, and it can be speculated that CPM responses are positively associated with the magnitude of placebo effects. Yet, no studies have tested this. METHODS: The study included 19 patients with neuropathic pain. CPM was quantified as the difference in pressure pain threshold (PPT) as measured at the middle deltoid muscle before and after 5-min exposure to the cold pressor test (CPT) (conditioning pain stimulus). Placebo effects were tested via open and hidden applications of the pain-relieving agent lidocaine (2 mL) using a disinfection napkin controlled for no treatment. RESULTS: The mean (SD) PPT was 668.7 (295.7) kPa before and 742.3 (370.8) kPa after the CPT. The mean (SD) CPM response was -73.6 (214.0) kPa corresponding to an 11% increase in PPT, reflecting a normally functioning endogenous pain modulatory system. Large and significant placebo effects were observed in ongoing neuropathic pain intensity (p = 0.002). The CPM response did not predict the magnitude of the placebo effect (p = 0.765). Moreover, there were no interaction effects for the moderator variables: clinical pain level (p = 0.136), age (p = 0.347) and gender (p = 0.691). CONCLUSIONS: Conditioned pain modulation and placebo effects do not seem to be associated in patients with neuropathic pain. SIGNIFICANCE: Conditioned pain modulation and placebo effects are endogenous pain-modulating phenomena that are influenced by some of the same mechanisms. This study suggests that CPM and placebo effects in neuropathic pain are independent phenomena that may be mediated by different mechanisms.

Structural and functional assessment of skin nerve fibres in small-fibre pathology.

Damage to nociceptor nerve fibres may give rise to peripheral neuropathies, some of which are pain free and some are painful. A hallmark of many peripheral neuropathies is the loss of small nerve fibres in the epidermis, a condition called small-fibre neuropathy (SFN) when it is predominantly the small nerve fibres that are damaged. Historically, SFN has been very difficult to diagnose as clinical examination and nerve conduction studies mainly detect large nerve fibres, and quantitative sensory testing is not sensitive enough to detect small changes in small nerve fibres. However, taking a 3-mm punch skin biopsy from the distal leg and quantification of the nerve fibre density has proven to be a useful method to diagnose SFN. However, the correlation between the nerve fibre loss and other test results varies greatly. Recent studies have shown that it is possible not only to extract information about the nerve fibre density from the biopsies but also to get an estimation of the nerve fibre length density using stereology, quantify sweat gland innervation and detect morphological changes such as axonal swelling, all of which may be additional parameters indicating diseased small fibres relating to symptoms reported by the patients. In this review, we focus on available tests to assess structure and function of the small nerve fibres, and summarize recent advances that have provided new possibilities to more specifically relate structural findings with symptoms and function in patients with SFN.

Pre-operative baroreflex sensitivity and efferent cardiac parasympathetic activity are correlated with post-operative pain.

BACKGROUND: A maladaptation of the autonomic nervous system may been seen in patients with chronic pain that includes persistent changes in the autonomic tone, increased heart rate, and reduced heart rate variability and baroreflex sensitivity. Baroreflex sensitivity and acute pain intensity have been reported to be inversely correlated. However, it is unknown whether the same correlation applies with regard to post-operative pain. In the present study, autonomic function was measured in patients scheduled for minor hand surgery and correlated with early and persistent pain after the procedure. Thus, the cause (autonomic imbalance) was present before the effect (post-operative pain). Our primary hypothesis was that a lower level of pre-operative baroreflex sensitivity is correlated with increased early post-operative pain. METHODS: There were 30 patients included and scheduled for open carpal tunnel surgery. Baroreflex sensitivity and heart rate variability were measured before surgery. Efferent cardiac parasympathetic activity was estimated by power spectral analysis of heart rate variability. Post-operative pain was recorded daily for 6 weeks (early post-operative pain) and for 1 week 1 year after surgery (persistent post-operative pain). RESULTS: Pre-operative baroreflex sensitivity correlated negatively with early (P=0.05) and persistent (P=0.04) post-operative pain. Efferent cardiac parasympathetic activity correlated negatively with early (P=0.03) but not persistent post-operative pain (P=0.12). CONCLUSIONS: The findings suggest that a low pre-operative level of baroreflex sensitivity is associated with higher post-operative pain intensity. To our knowledge, this is the first study to show the correlation between baroreflex sensitivity and post-operative pain.

Chronic pain after inguinal hernia repair in children.

BACKGROUND: The prevalence of moderate-to-severe pain after inguinal hernia repair (IHR) in adults is ≈ 10%. Two studies with very long follow-up periods (16.8 and 49 yr, respectively) have, however, suggested that the risk of developing chronic pain is much lower in children. The purpose of the present study was to examine the prevalence of chronic pain 6-48 months after IHR in children. METHODS: Postal questionnaires were sent to 156 children who had undergone IHR between the age of 6 months and 12 yr. The children were asked to recall the duration of postoperative pain, if necessary with help from their parents, and to describe the intensity and character of their pain, if the pain was still present. Children with chronic pain were offered quantitative sensory testing (QST), and a surgical examination, including ultrasound, in order to exclude hernia recurrence. RESULTS: Ninety-eight children, mean (sd) age 7.8 (2.6) yr, answered the questionnaire. Their age at the time of surgery was mean (sd) 4.6 (2.4) yr, and the follow-up period was mean (sd) 3.2 (1.3) yr. Five children (5.1%, 95% confidence interval: 0.75-9.5) had pain located in the inguinal region, and three of these children underwent further examination. There was no hernia recurrence, but QST revealed pinprick hyperalgesia and decreased pressure pain thresholds on the operated side in all three children. CONCLUSIONS: The prevalence of chronic pain after IHR in children is 5.1%, which is lower than the prevalence reported after adult hernia repair.

Acute and chronic pain: where we are and where we have to go.

In recent years, increasing attention has been focused on the treatment of acute and chronic pain with a considerable number of publications about it. Nevertheless all the attention focused on it, the evidence of pain treatments is still unfolding, and occasionally conflicting. Hence it is still necessary that we point out our research efforts in trying to obtain a better understand of pathophysiology of pain and of real efficacy and safety of acute and chronic pain treatments. Our goal with this review is to summarize the latest research trends and the most advanced therapeutic standards for pain syndromes described in the literature, the discussion will be divided in four main topics, as these topics were treated during the SIMPAR (Study In Multidisciplinary PAin Research) meeting, held on December 2010 in Pavia: pathophysiology of pain, acute postoperative pain, opioids and pain, and chronic pain (Failed Back Surgery Syndrome). In the chapter of pathophysiology of pain we analyzed how to obtain a more personalized treatment through the study of the genetic and neurophysiological characteristics of patients and how to select the right local anesthetic according to anatomic and metabolizing patterns of patients. In acute postoperative pain we focalized our attention on the evidence supporting the use of continuous peripheral nerve blocks in the treatment of postoperative pain and in the prevention of chronic persistent post-operative pain, with a special attention in preventing side effects of regional anesthesia. We also reviewed the current evidence about the use of new very interesting modality to control postoperative pain after laparoscopy: pre-emptive nebulization of local anesthetic in abdominal cavity. As opioids are currently widely used to control chronic oncologic and non-oncologic pain, in this review we analyzed the level of evidence for their use, how to manage them better and psychological factors that can affect their success and/or determine addiction. Finally, we summarized the current evidence about Failed Back Surgery Syndrome focalizing our attention both in diagnosing it correctly and treating this syndrome with specific knowledge of the anatomic space that we have to approach and applying the possible treatments depending on pain pathophysiology and patient characteristics. In conclusion, it is important to try to personalize even better the therapy of patients with acute and chronic pain through a more accurate knowledge of anatomy, pathophysiology of pain, pharmacokinetic of pain drugs and of new device/therapies available.

Heterozygous deletion at the RLN1 locus in a family with testicular germ cell cancer identified by integrating copy number variation data with phenome and interactome information.

To search for disease-related copy number variations (CNVs) in families with a high frequency of germ cell tumours (GCT), we analysed 16 individuals from four families by array comparative genomic hybridization (aCGH) and applied an integrative systems biology algorithm that prioritizes risk-associated genes among loci targeted by CNVs. The top-ranked candidate, RLN1, encoding a Relaxin-H1 peptide, although only detected in one of the families, was selected for further investigations. Validation of the CNV at the RLN1 locus was performed as an association study using qPCR with 106 sporadic testicular GCT patients and 200 healthy controls. Observed CNV frequencies of 1.9% among cases and 1.5% amongst controls were not significantly different and this was further confirmed by CNV data extracted from a genome-wide analysis of 189 cases and 380 controls, where similar frequencies of 2.2% were observed in both groups (p=1). Immunohistochemistry for Relaxin-H1 (RLN1), Relaxin-H2 (RLN2) and their cognate receptor, RXFP1, detected one, and in some cases both, of the relaxins in Leydig cells, Sertoli cells and a subset of neoplastic germ cells, whereas the receptor was present in Leydig cells and spermatids. Collectively, the findings show that a heterozygous loss at the RLN1 locus is not a genetic factor mediating high population-wide risk for testicular germ cell tumour, but do not exclude a contribution of this aberration in some cases of cancer. The preliminary expression data suggest a possible role of the relaxin peptides in spermatogenesis and warrant further studies.

Consequences of persistent pain after lung cancer surgery: a nationwide questionnaire study.

BACKGROUND: post-thoracotomy pain syndrome (PTPS) and its social consequences have been inconsistently investigated as most studies were either small sized, focused on a limited number of risk factors or included heterogeneous surgical procedures. The current objectives were to obtain detailed information on the consequences of PTPS after thoracotomy and video-assisted thoracic surgery (VATS) from homogenous unselected nationwide data, and to suggest mechanisms for the development of PTPS. METHODS: data from 1327 patients were collected using a prospective national database and combined with a detailed questionnaire. RESULTS: the response rate was 81.5%, resulting in 546 patients without prior thoracic surgery for the final analysis. Follow-up was 22 months (range 12-36). PTPS occurred in 33% thoracotomy patients and 25% VATS patients. Clinically relevant pain was present in 11-18% of the patients and severe pain in 4-12% depending on the level of physical activity. In PTPS patients, 64% also had pain from other locations on the body. Perceived sensory changes in the thoracic area were present in 63% of PTPS patients vs. 25% in pain-free patients (P<0.001). When comparing VATS with thoracotomy, no consistent differences in the prevalence, distribution of pain, sensory changes or effect of pain on daily activities were observed although clinically relevant and severe pain was reduced after VATS. CONCLUSIONS: this nationwide study corroborates that PTPS is a clinically relevant problem influencing daily activities a long time after thoracotomy and VATS. Nerve injury and increased pain responsiveness may explain the majority of symptoms, the prevalence and distribution of pain including perceived sensory sensations.

EFNS guidelines on neuropathic pain assessment: revised 2009.

BACKGROUND AND PURPOSE: We have revised the previous EFNS guidelines on neuropathic pain (NP) assessment, which aimed to provide recommendations for the diagnostic process, screening tools and questionnaires, quantitative sensory testing (QST), microneurography, pain-related reflexes and evoked potentials, functional neuroimaging and skin biopsy. METHODS: We have checked and rated the literature published in the period 2004-2009, according to the EFNS method of classification for diagnostic procedures. RESULTS: Most of the previous recommendations were reinforced by the new studies. The main revisions relate to: (i) the new definition of NP and a diagnostic grading system; (ii) several new validated clinical screening tools that identify NP components, and questionnaires which assess the different types of NP; (iii) recent high-quality studies on laser-evoked potentials (LEPs) and skin biopsy. CONCLUSIONS: History and bedside examination are still fundamental to a correct diagnosis, whilst screening tools and questionnaires are useful in indicating probable NP; QST is also useful for indicating the latter, and to assess provoked pains and treatment response. Amongst laboratory tests, LEPs are the best tool for assessing Adelta pathway dysfunction, and skin biopsy for assessing neuropathies with distal loss of unmyelinated nerve fibres.

Country-specific chemical signatures of persistent environmental compounds in breast milk.

Recent reports have confirmed a worldwide increasing trend of testicular cancer incidence, and a conspicuously high prevalence of this disease and other male reproductive disorders, including cryptorchidism and hypospadias, in Denmark. In contrast, Finland, a similarly industrialized Nordic country, exhibits much lower incidences of these disorders. The reasons behind the observed trends are unexplained, but environmental endocrine disrupting chemicals (EDCs) that affect foetal testis development are probably involved. Levels of persistent chemicals in breast milk can be considered a proxy for exposure of the foetus to such agents. Therefore, we undertook a comprehensive ecological study of 121 EDCs, including the persistent compounds dioxins, polychlorinated biphenyls (PCBs), pesticides and flame retardants, and non-persistent phthalates, in 68 breast milk samples from Denmark and Finland to compare exposure of mothers to this environmental mixture of EDCs. Using sophisticated, bioinformatic tools in our analysis, we reveal, for the first time, distinct country-specific chemical signatures of EDCs with Danes having generally higher exposure than Finns to persistent bioaccumulative chemicals, whereas there was no country-specific pattern with regard to the non-persistent phthalates. Importantly, EDC levels, including some dioxins, PCBs and some pesticides (hexachlorobenzene and dieldrin) were significantly higher in Denmark than in Finland. As these classes of EDCs have been implicated in testicular cancer or in adversely affecting development of the foetal testis in humans and animals, our findings reinforce the view that environmental exposure to EDCs may explain some of the temporal and between-country differences in incidence of male reproductive disorders.

Chronic pain in adults after thoracotomy in childhood or youth.

BACKGROUND: Chronic pain is common after thoracotomy with reported prevalence rates of 20-60%. The pain may be caused by damage to the intercostal nerves during surgery. Some studies have suggested that young age at the time of surgery reduces the risk of developing chronic pain. So far, no studies have examined if children and adolescents develop chronic pain after thoracotomy. METHODS: Eighty-eight patients, mean (sd) age 39.3 (7.7) yr, who underwent thoracotomy between the age of 0 and 25 yr were asked to recall the duration of postoperative pain and-if pain was still present-to describe intensity and character of pain. In addition, all patients underwent quantitative sensory testing. RESULTS: Fourteen patients (16%) recalled that their postoperative pain had lasted for more than 3 months: one (3.2%) patient in the youngest group (0-6 yr), seven (19.4%) patients in the age group 7-12 yr, and six (28.5%) patients in the age group 13-25 yr (P=0.03). Three out of the 14 patients, who were 11, 11, and 18 yr of age at the time of surgery, still had pain at present. Quantitative sensory testing revealed hypo- and hyperphenomena in most patients, including those with persistent pain. Tactile detection thresholds and pressure detection thresholds were significantly higher on the operated side when compared with the contralateral side (n=88; P<0.001). CONCLUSIONS: The risk of developing chronic pain after thoracotomy seems to be lower if surgery is performed at a young age. Pain after thoracotomy is likely to be of neuropathic origin.

Incidence of symptoms and signs of TMD following third molar surgery: a controlled, prospective study.

The purpose of this prospective study was to investigate if third molar surgery is associated with the development of symptoms and signs of temporomandibular disorders (TMD) during a 6-month post-operative observation period using the Research Diagnostic Criteria for TMD (RDC/TMD) instrument. Seventy-two subjects eligible for third molar surgery under local anaesthesia (patients) were included. Patients were examined according to the RDC/TMD instrument at baseline, 1 week, 1 and 6 months after surgery. Twenty-five age- and sex-matched healthy non-operative control subjects (controls) were included and examined at baseline and at 6 months. In the patient group, we found: (i) reduced range of maximum jaw opening at one week after surgery (P < 0.001), (ii) increased characteristic pain intensity 1 week after surgery (P < 0.05), (iii) increased disability up to 1 month after surgery (P < 0.05), (iv) increased incidence of muscle pain on palpation up to 6 months after surgery (P < 0.05), (v) increased incidence of pain on palpation of the temporomandibular joint up to 6 months after surgery (P < 0.05) and (vi) increased incidence of painful TMD 6 months after surgery. But, when compared with untreated controls, subjects undergoing third molar surgery have a statistically insignificant increased incidence of TMD 6 months post-operatively.

Chronic pain after hysterectomy.

BACKGROUND: Chronic pain is a well-known adverse effect of surgery, but the risk of chronic pain after gynaecological surgery is less established. METHOD: This review summarizes studies on chronic pain following hysterectomy. The underlying mechanisms and risk factors for the development of chronic post-hysterectomy pain are discussed. RESULTS AND CONCLUSION: Chronic pain is reported by 5-32% of women after hysterectomy. A guideline is proposed for future prospective studies.

Modic changes, possible causes and relation to low back pain.

UNLABELLED: In patients with low back pain (LBP) it is only possible to diagnose a small proportion, (approximately 20%), on a patho-anatomical basis. Therefore, the identification of relevant LBP subgroups, preferably on a patho-anatomical basis, is strongly needed. Signal changes on MRI in the vertebral body marrow adjacent to the end plates also known as Modic changes (MC) are common in patients with LBP (18-58%) and is strongly associated with LBP. In asymptomatic persons the prevalence is 12-13%. MC are divided into three different types. Type 1 consists of fibro vascular tissue, type 2 is yellow fat, and type 3 is sclerotic bone. The temporal evolution of MC is uncertain, but the time span is years. Subchondral bone marrow signal changes associated with pain can be observed in different specific infectious, degenerative and immunological diseases such as osseous infections, osteoarthritis, ankylosing spondylitis and spondylarthritis. In the vertebrae, MC is seen in relation to vertebral fractures, spondylodiscitis, disc herniation, severe disc degeneration, injections with chymopapain, and acute Schmorl's impressions. The aim of this paper is to propose two possible pathogenetic mechanisms causing Modic changes. These are: A mechanical cause: Degeneration of the disc causes loss of soft nuclear material, reduced disc height and hydrostatic pressure, which increases the shear forces on the endplates and micro fractures may occur. The observed MC could represent oedema secondary to the fracture and subsequent inflammation, or a result of an inflammatory process from a toxic stimulus from the nucleus pulposus that seeps through the fractures. A bacterial cause: Following a tear in the outer fibres of the annulus e.g. disc herniation, new capilarisation and inflammation develop around the extruded nuclear material. Through this tissue it is possible for anaerobic bacteria to enter the anaerobic disc and in this environment cause a slowly developing low virulent infection. The MC could be the visible signs of the inflammation and oedema surrounding this infection, because the anaerobic bacteria cannot thrive in the highly aerobic environment of the MC type 1. PERSPECTIVES: One or both of the described mechanisms can - if proven - be of significant importance for this specific subgroup of patients with LBP. Hence, it would be possible to give a more precise and relevant diagnosis to 20-50% of patients with LBP and enable in the development of efficient treatments which might be antibiotics, special rehabilitation programmes, rest, stabilizing exercise, or surgical fixation, depending on the underlying cause for the MC.

EFNS guidelines on neurostimulation therapy for neuropathic pain.

Pharmacological relief of neuropathic pain is often insufficient. Electrical neurostimulation is efficacious in chronic neuropathic pain and other neurological diseases. European Federation of Neurological Societies (EFNS) launched a Task Force to evaluate the evidence for these techniques and to produce relevant recommendations. We searched the literature from 1968 to 2006, looking for neurostimulation in neuropathic pain conditions, and classified the trials according to the EFNS scheme of evidence for therapeutic interventions. Spinal cord stimulation (SCS) is efficacious in failed back surgery syndrome (FBSS) and complex regional pain syndrome (CRPS) type I (level B recommendation). High-frequency transcutaneous electrical nerve stimulation (TENS) may be better than placebo (level C) although worse than electro-acupuncture (level B). One kind of repetitive transcranial magnetic stimulation (rTMS) has transient efficacy in central and peripheral neuropathic pains (level B). Motor cortex stimulation (MCS) is efficacious in central post-stroke and facial pain (level C). Deep brain stimulation (DBS) should only be performed in experienced centres. Evidence for implanted peripheral stimulations is inadequate. TENS and r-TMS are non-invasive and suitable as preliminary or add-on therapies. Further controlled trials are warranted for SCS in conditions other than failed back surgery syndrome and CRPS and for MCS and DBS in general. These chronically implanted techniques provide satisfactory pain relief in many patients, including those resistant to medication or other means.

Chronic pain following total hip arthroplasty: a nationwide questionnaire study.

BACKGROUND: Chronic post-operative pain is a well-recognized problem after various types of surgery, but little is known about chronic pain after orthopedic surgery. Severe pre-operative pain is the primary indication for total hip arthroplasty (THA). Therefore, we examined the prevalence of chronic pain after THA in relation to pre-operative pain and early post-operative pain. METHODS: A questionnaire was sent to 1231 consecutive patients who had undergone THA 12-18 months previously, and whose operations had been reported to the Danish Hip Arthroplasty Registry. RESULTS: The response rate was 93.6%. Two hundred and ninety-four patients (28.1%) had chronic ipsilateral hip pain at the time of completion of the questionnaire, and pain limited daily activities to a moderate, severe or very severe degree in 12.1%. The chronic pain state was related to the recalled intensity of early post-operative pain [95% confidence interval (CI), 20.4-33.4%] and pain complaints from other sites of the body (95% CI, 20.7-32.1%), but not to the pre-operative intensity of pain. CONCLUSION: Chronic pain after THA seems to be a significant problem in at least 12.1% of patients. Our results suggest that genetic and psychosocial factors are important for the development of chronic post-THA pain.

Ascitic complement system in ovarian cancer.

Ovarian cancer spreads intraperitoneally and forms fluid, whereby the diagnosis and therapy often become delayed. As the complement (C) system may provide a cytotoxic effector arm for both immunological surveillance and mAb-therapy, we have characterised the C system in the intraperitoneal ascitic fluid (AF) from ovarian cancer patients. Most of the AF samples showed alternative and classical pathway haemolytic activity. The levels of C3 and C4 were similar to or in the lower normal range when compared to values in normal sera, respectively. However, elevated levels of C3a and soluble C5b-9 suggested C activation in vivo. Malignant cells isolated from the AF samples had surface deposits of C1q and C3 activation products, but not of C5b-9 (the membrane attack complex; MAC). Activation could have become initiated by anti-tumour cell antibodies that were detected in the AFs and/or by changes on tumour cell surfaces. The lack of MAC was probably due to the expression of C membrane regulators CD46, CD55 and CD59 on the tumour cells. Soluble forms of C1 inhibitor, CD59 and CD46, and the alternative pathway inhibitors factor H and FHL-1 were present in the AF at concentrations higher than in serum samples. Despite the presence of soluble C inhibitors it was possible to use AF as a C source in antibody-initiated killing of ovarian carcinoma cells. These results demonstrate that although the ovarian ascitic C system fails as an effective immunological surveillance mechanism, it could be utilised as an effector mechanism in therapy with intraperitoneally administrated mAbs, especially if the intrinsic C regulators are neutralised.

Therapeutic outcome in neuropathic pain: relationship to evidence of nervous system lesion.

Treatment outcome in patients with neuropathic pain (NP) is often variable and disappointing. We tested the hypothesis that patients with clear evidence of nervous system lesion respond better to pharmacological treatment with documented effect on NP than patients with poor or no evidence of nervous system lesion. Furthermore, we examined whether specific symptoms or signs were associated with treatment outcome. A total of 214 patients with suspected non-cancer NP were divided into four groups with graded evidence of nervous system lesion based on medical history, bedside sensory examination, quantitative sensory tests, electrophysiology, and neuroimaging. Patients were treated with imipramine guided by plasma-drug concentrations. Gabapentin 2400 mg/day was given in case of treatment failure or if imipramine treatment was not possible. Two hundred patients completed the study. Global pain relief was similar in the four groups. There was no association between evidence of nervous system lesion and treatment outcome. Classical NP signs: abnormal temporal summation, cold and brush allodynia, and abnormal sensibility to temperature were also unrelated to outcome. Treatment outcome was similar in peripheral and central definite NP. Neither definite evidence of nervous system lesion nor abnormal sensory phenomena seems to predict for good outcome of therapy with imipramine or gabapentin in patients with suspected neuropathic pain.

Chronic pain following Caesarean section.

BACKGROUND: Chronic postoperative pain is a well-recognized problem after various types of surgery such as amputation, thoracotomy, mastectomy, gallbladder surgery and inguinal hernia repair. However, little is known about chronic pain after gynaecologic surgery. Therefore, the aim was to study the incidence of chronic pain after Caesarean section. METHODS: A questionnaire was sent in February/March 2003 to 244 consecutive patients who underwent Caesarean section in a one-year period from 1 October 2001 to 30 September 2002. Patients were asked about duration of postoperative abdominal scar pain, and if pain was still present to describe the frequency and intensity of pain and its impact on daily life. The questionnaire also included questions about the Caesarean section and about pain problems elsewhere. RESULTS: A total of 220 patients (90.2%) answered the questionnaire. The mean follow-up time was 10.2 months (range 6-17.6). Postoperative pain resolved in most patients within 3 months but 27 patients (12.3%) still had pain at the time of the interview. No patients had constant pain, but in 13 of 27 patients (5.9%) pain was present daily or almost daily. Patients with persistent pain (n = 27) had more often undergone general than spinal anaesthesia for the Caesarean section. Frequencies of pain problems elsewhere and recalls of severe acute postoperative pain were also higher among patients with persistent pain. CONCLUSION: Chronic pain after Caesarean section seems to be a significant problem in at least 5.9% of patients.