Therapy improvement in two out-patient mental health clinics

This study describes clients, therapists, treatment characteristics, and therapy outcomes for 551 consecutive, first-time clients at two out-patient mental health clinics. Significant improvement was found on target problems, global outcome ratings, and Hopkins Symptom Checklist scores for clients who mutually terminated therapy. The target problem and outcome ratings remained higher for this group than for dropouts at a six-month follow-up interview. Clients who improved most were those who were initially most uncomfortable and disturbed. Improvement was also strongly related to the number of therapy sessions. The implications of these and other results are discussed.     

Preimplantation genetic screening: a survey of in vitro fertilization clinics

PurposeThe purpose of this study was to determine which US in vitro fertilization clinics provide preimplantation genetic screening for aneuploidy in treating infertility, and to explore clinic directors' attitudes toward this technique.MethodsOnline survey included 415 US assisted reproductive technology clinics. The survey had a valid response rate of 45% or 186 clinics.ResultsNearly 68% of US in vitro fertilization clinics responding to the survey provided preimplantation genetic screening in an effort to increase success rates of fertility treatment. More than half of these in vitro fertilization clinics (56%) provided preimplantation genetic screening for advanced maternal age and the same percentage provided preimplantation genetic screening to treat repeated in vitro fertilization failure, whereas 66% provided preimplantation genetic screening to treat women with repeated miscarriage. Opinions of the effectiveness of preimplantation genetic screening for these indications varied widely, even among those providing it. Most directors (85%) of clinics providing preimplantation genetic screening believed that more data are needed to determine whether and to whom it should be offered.ConclusionsDespite the lack of data supporting the use of preimplantation genetic screening for recurrent pregnancy loss, in vitro fertilization failure, and advanced maternal age, a majority of in vitro fertilization clinics in the United States offer preimplantation genetic screening for these purposes. There is significant support among clinic directors for more research into the effectiveness of preimplantation genetic screening and for professional guidelines in this area.     

Controlling neuropathic pain in HIV

Neuropathic pain is associated with numerous systemic illnesses, including HIV infection. The diagnosis and management of peripheral neuropathy presents diagnostic and therapeutic challenges. Among various forms of HIV-associated peripheral neuropathies, distal symmetrical polyneuropathy (DSP) is the most common. DSP may be caused or exacerbated by neurotoxic antiretrovirals, particularly the dideoxynucleoside analogues (d-drugs). Selection of appropriate pharmacologic intervention for peripheral neuropathy should be based on efficacy, safety, ease of administration, and cost. We review treatment options for painful HIV neuropathy, including experimental agents studied in recent and ongoing clinical trials.     

神经病理性疼痛的免疫机制

研究发现,在中枢神经系统及外周神经系统中,免疫细胞和分子在神经病理性疼痛过程中发挥着越来越重要的作用,对传统的以神经元为中心的疼痛理论发起了挑战。神经损伤后外周的肥大细胞、中性粒细胞、巨噬细胞和T淋巴细胞等免疫细胞所产生的级联炎性反应以及胶质细胞的激活是神经病理性疼痛形成和维持的关键因素,这些免疫细胞通过释放大量炎性介质最终导致疼痛的产生。     

Inhibition of neuropathic pain by a potent disintegrin--triflavin

Injury to peripheral nerves may result in severe and intractable neuropathic pain. Many efforts have been focused on the elucidation of the mechanisms of neuropathic pain. It was found here that integrin plays an important role in the induction of neuropathic pain and treatment of disintegrin is able to attenuate neuropathic pain. The rats were induced hyperalgesia by tightly ligating the L5 spinal nerve and cut just distal to the ligature on one side. Mechanical and thermal stimuli were applied in the middle dermatome of the hind paw. Epidural administration of triflavin (TFV), an arginine-glycine-aspartic acid (RGD) containing disintegrin, inhibited hyperalgesia induced by either mechanical or thermal stimulation. Immunohistochemistry showed that the sprouting of sympathetic nerves into DRG by neuropathic surgery was markedly inhibited by TFV. Beta 1 integrin mRNA of L5 DRG increased immediately 1 day after tight ligation and cut of L5 spinal nerve. However, beta 1 integrin mRNA in uninjured L4 DRG increased later on Day 3 after surgery. On the other hand, alpha-CGRP precursor mRNA decreased in ipsilateral L5 DRG but increased in L4 DRG after neuropathic surgery. Immunohistochemistry shows that beta 3 integrins of L5 as well as L4 increased in response to neuropathic surgery and administration of triflavin antagonized the increasing action. These results suggest that there is interaction between injured and uninjured neurons and the induction of neuropathic pain is related to neuronal sprouting. Disintegrin is able to inhibit neuronal sprouting and the induction of hyperalgesia induced by peripheral nerve injury and may thus be a new category of drugs to be developed for the treatment of neuropathic pain.     

Importance of sleep in neuropathic pain

This brief review is intended to provide an overview of the importance of disturbed or non-restorative sleep in patients with neuropathic pain. Disturbed sleep is common in neuropathic pain and along with co-morbid anxiety and depression can have profound effects on daytime functioning and quality of life of the patient. It is thus important that the treatment of neuropathic pain should also seek to diagnose and appropriately treat these co-morbidities in order to optimally improve the patient??s functioning.     

Purinoceptors in microglia and neuropathic pain

Emerging evidence indicates that microglia play a critical role in the pathogenesis of neuropathic pain, a debilitating chronic pain condition that can occur after peripheral nerve damage caused by disease, infection, or physical injury. Microglia are immunocompetent cells of the central nervous system and express various ionotropic P2X and metabotropic P2Y purinoceptors. After injury to a peripheral nerve, microglia in the spinal cord become activated and upregulate expression of the P2X4 receptor. Recent findings suggest that activation of P2X4 receptors evokes release of brain-derived neurotrophic factor from microglia and that this mediates microglia–neuron signaling leading to pain hypersensitivity. Thus, P2X4 receptors and the intracellular signaling mediators in microglia are promising therapeutic targets for the development of novel pharmacological agents in the management of neuropathic pain.     

Disinfection methods in general practice and health authority clinics: a telephone survey

Concern about the epidemic of the acquired immune deficiency syndrome led to discussions in one health district about the dangers of cross-infection from instruments in general practice and health authority clinics. In order to establish what current disinfection practices were in use a telephone survey was adopted as a quick and easy method of data collection. Information was collected on who was responsible for disinfection as well as details of how each instrument was disinfected. Results from 69 general practices and 21 health authority clinice in one health district are reported.

Some form of sterilizer was used in 63 general practices. These included water boilers (49%), dry heat sterilizers (41%), autoclaves (5%) and pressure cookers (5%). Sixty one practices were using metal vaginal specula and of these 29 were disinfecting by boiling, three were using pressure cookers, 18 dry heat, seven chemical methods, three autoclaves and one the central sterile department of the local hospital. Of those who were boiling after simple washing, three practices boiled for five to 10 minutes and reused instruments during the same clinic. Of the 29 using simple boiling 20 (69%) were boiling for less than 20 minutes.

The study highlights the fact that no formal advice has been given on disinfection practice by the DHSS, the health authorities or the family practitioner committees. The need to set up local guidelines and develop practical steps for their introduction are discussed.

     

Crossed-withdrawal reflex in a rat model of neuropathic pain: implications in neural plasticity

Recently we developed a neuropathic rat model employing a distal sciatic nerve branch injury, in which rats show vigorous behavioral signs of neuropathic pain. This study was performed to evaluate the crossed-withdrawal reflex in which any stimuli applied to the uninjured side produces allodynic signs on the injured side in our neuropathic pain model. Rats that received neuropathic surgery developed behavioral signs of neuropathic pain. In addition, these rats developed pain responses of the injured paw to stimuli applied to the contralateral uninjured paw, therefore, demonstrating 'the crossed-withdrawal reflex.' Moreover, electrical stimulation of the uninjured paw developed evoked potentials in the ventral root on the injured side. These results suggest that information processing from input on the uninjured side to output on the injured side, can be facilitated in rats with a nerve injury and that neuroplasticity may contribute to the crossed-withdrawal reflex.     

Enhanced production of monocyte chemoattractant protein-1 in the dorsal root ganglia in a rat model of neuropathic pain: possible involvement in the development of neuropathic pain

Chemokines are a family of peptides originally identified as the factors regulating the migration of leukocytes in inflammatory and immune responses. Recently, they have been shown to be produced in the central and peripheral nervous systems under various pathological conditions and act on neuronal and glial cells. In this study, we examined the production of monocyte chemoattractant protein-1 (MCP-1), a well-characterized chemokine, in dorsal root ganglia (DRG) in a rat model of neuropathic pain. Partial ligation of the sciatic nerve induced mechanical allodynia in the ipsilateral hindpaw with weaker allodynia in the contralateral one. Immunohistochemical analyses revealed that the number of MCP-1 immunoreactivity (ir)-positive cells was increased in the ipsilateral DRG. The increase started by 4h after the ligation, peaked at 24h and continued to at least 48 h. The weaker but significant increase was observed in the contralateral DRG. Double immunofluorescent staining demonstrated that almost all of the MCP-1ir-positive cells were neuronal cells. In situ hybridization histochemistry showed that MCP-1 mRNA expression was markedly upregulated in the ipsilateral DRG with weaker increase in the contralateral one at 24 h after the ligation, indicating that the elevation in MCP-1ir detected by immunohistochemistry was due to an upregulation of MCP-1 production by the DRG neurons themselves. Furthermore, intrathecal administration of MCP-1 induced mechanical allodynia. These results suggest that MCP-1 produced in the DRG neurons is involved in the development of mechanical allodynia induced by nerve injury.     

Effects of α-tocopherol in rats with a neuropathic pain syndrome

The rat model of a neuropathic pain syndrome (transection of the sciatic nerve with encapsulation of its central end) was used to evaluate the efficacy of the antioxidant α-tocopherol in such syndromes. It was found that administration of α-tocopherol 3 days before nerve transection and then for 3 weeks thereafter it delayed the development of the pain syndrome, which subsequently tended to subside. In contrast, a 3-week α-tocopherol treatment started when the pain syndrome had already set in failed to influence its evolution. α-Tocopherol markedly reduced manifestations of inflammatory and degenerative processes in the denervated limb. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 8, pp. 123–125, August, 1994 Presented by G. N. Kryzhanovskii, Member of the Russian Academy of Medical Sciences     

Different pattern of pleiotrophin and midkine expression in neuropathic pain: Correlation between changes in pleiotrophin gene expression and rat strain differences in neuropathic pain

Pleiotrophin (PTN) and midkine (MK) are two growth factors highly redundant in function that exhibit neurotrophic actions and are upregulated at sites of nerve injury, both properties being compatible with a potential involvement in the pathophysiological events that follow nerve damage (i.e. neuropathic pain). We have tested this hypothesis by comparatively studying PTN and MK gene expression in the spinal cord and dorsal root ganglia (DRG) of three rat strains known to differ in their behavioural responses to chronic constriction injury (CCI) of the sciatic nerve: Lewis, Fischer 344 (F344) and Sprague–Dawley (SD). Real time RT-PCR revealed minimal changes in PTN/MK gene expression in the spinal cord after CCI despite the strain considered, but marked changes were detected in DRG. A significant upregulation of PTN gene expression occurred in injured DRG of the F344 strain, the only strain that recovers from CCI-induced mechanical allodynia 28 days after surgery. In contrast, PTN was found to be downregulated in injured DRG of SD rats, the most sensitive strain in behavioural studies. These changes in PTN were not paralleled by concomitant modifications of MK gene expression. The results demonstrate previously unidentified differences between PTN and MK patterns of expression. Furthermore, the data suggest that upregulation of PTN, but not MK, could play an important role in the recovery from CCI.     

Different pattern of pleiotrophin and midkine expression in neuropathic pain: correlation between changes in pleiotrophin gene expression and rat strain differences in neuropathic pain

Pleiotrophin (PTN) and midkine (MK) are two growth factors highly redundant in function that exhibit neurotrophic actions and are upregulated at sites of nerve injury, both properties being compatible with a potential involvement in the pathophysiological events that follow nerve damage (i.e. neuropathic pain). We have tested this hypothesis by comparatively studying PTN and MK gene expression in the spinal cord and dorsal root ganglia (DRG) of three rat strains known to differ in their behavioural responses to chronic constriction injury (CCI) of the sciatic nerve: Lewis, Fischer 344 (F344) and Sprague-Dawley (SD). Real time RT-PCR revealed minimal changes in PTN/MK gene expression in the spinal cord after CCI despite the strain considered, but marked changes were detected in DRG. A significant upregulation of PTN gene expression occurred in injured DRG of the F344 strain, the only strain that recovers from CCI-induced mechanical allodynia 28 days after surgery. In contrast, PTN was found to be downregulated in injured DRG of SD rats, the most sensitive strain in behavioural studies. These changes in PTN were not paralleled by concomitant modifications of MK gene expression. The results demonstrate previously unidentified differences between PTN and MK patterns of expression. Furthermore, the data suggest that upregulation of PTN, but not MK, could play an important role in the recovery from CCI.     

大麻素受体2参与神经病理性疼痛的研究进展

神经病理性疼痛(Neuropathic Pain)是由于躯体感觉系统产生疾病或受到者损伤后,机体受到的有害或者无害的刺激被病理性的放大后所致.周围神经性痛是起源于周围神经系统受到机械创伤、代谢性疾病、神经化学毒物等影响.而中枢神经性痛一般都是由于脊髓损伤、中风或者多发性硬化引起的[1].然而到目前为止,神经病理性痛确切的发病机制仍不清楚,临床上治疗神经病理性疼痛的措施仍停留在对于原发疾病或损害的处理上,而现有的一些药物治疗(如阿片类药物、抗抑郁药和抗惊厥药物等),存在疼痛缓解不足或一些有害的副作用,药物用量受到限制,治疗效果一直不佳.近年来有研究表明大麻素受体2 (cannabinoid receptor 2,CB2)在选择性激动剂激活下能够有效地抑制急性、炎性疼痛而不产生中枢神经系统的副作用[2-5],因此其可能作为未来治疗神经病理性疼痛的一个治疗靶点.关于大麻素受体2在神经病理性疼痛中的作用的报道也越来越多,本文对其近几年的研究进展综述如下.     

Suppression of enriched environment-induced neurogenesis in a rodent model of neuropathic pain

Exposure to an enriched environment (EE) enhances neurogenesis and regulates emotionality. Previous reports have revealed that the rate of neurogenesis can be influenced by various environmental, endocrine, and pharmacologic stimuli. Chronic pain is a debilitating disease state characterized by complex alterations in both peripheral and central nociceptive pathways. In the present study, we evaluated the effect of chronic pain on environmental enrichment-induced hippocampal neurogenesis. Nerve-ligated mice were housed either in a standard environment or in the EE for 4 weeks. EE increased the immunoreactivity for doublecortin (DCX), a marker for immature neuron-positive cells, in the dentate gyrus (DG). Furthermore, the number of NeuroD (a neurogenic basic helix-loop-helix factor)-positive cells, in the DG was clearly increased by EE. Under these conditions, chronic pain suppressed enriched environment-mediated induction of both DCX- and NeuroD-labeled cells. These results suggest that chronic pain has stress-like damaging modulatory effects on hippocampal neurogenesis.     

Anti-allodynic efficacy of botulinum neurotoxin A in a model of neuropathic pain

Fyn, a member of the Src-family protein tyrosine kinase (PTK), is an essential factor in myelination in the CNS and is involved in murine embryonic stem (ES) cell growth and differentiation. Although dysfunctions of Fyn have been comparatively studied, the gain of function by ectopic expression, especially using ES cells, has seldom been investigated. In this article, we give the first report of the involvement of Fyn alteration in the sphere formation ability of murine ES cells. First, transient transfection of Fyn hardly affected multiplication and specialization. Then, we investigated Fyn overexpression using ES cells, which stably express Fyn. As a result, altered sphere formation capability was observed in all clones stably expressing Fyn. These results may provide important information for reproduction medical treatment using ES cells.