Spinal estrogen receptor alpha mediates estradiol-induced pronociception in a visceral pain model in the rat

We previously reported that 17β-estradiol (E2) is pronociceptive in a visceral pain model in the rat. Subcutaneously (s.c.) administered E2 reversed the decrease in the colorectal distention (CRD)-evoked visceromotor response produced by ovariectomy (OVx) and CRD-induced nociceptive responses were greater in proestrous rats compared with met/diestrous rats. The site of action, the type of estrogen receptors activated, and the possible intracellular signaling pathway involved are yet to be established. In the present study, intrathecal (i.t.) E2 administered to OVx rats mimicked the effects of s.c. E2, suggesting that spinal estrogen receptors are involved. This is further supported by the observations that the anti-estrogen ICI 182,780 injected i.t. in intact female rats significantly decreased the visceromotor response to CRD, the response of colonic afferents was not affected by OVx, and colonic afferents did not label for estrogen receptor α (ERα). The ERα selective agonist, 4,4′,4′′-[4-propyl-(1H)-pyrazole-1,3,5-triyl]tris-phenol (PPT; s.c. or i.t.) facilitated the visceromotor response similar to E2, suggesting ERα activation is involved in mediating the pronociceptive effect of E2. PPT (s.c. or i.t.) increased the response of spinal dorsal horn neurons to CRD, indicating a spinal site of action. In addition, s.c. E2 or PPT increased CRD-induced spinal extracellular signal-regulated kinase (ERK) phosphorylation that was not observed in OVx rats and a mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor blocked facilitation of the visceromotor response by PPT. Taken together, the present study demonstrates that spinal ERα mediates the pronociceptive effect of E2 on visceral signal processing through activation of the MAPK pathway.     

Management of acute lumbar disk herniation initially presenting as mechanical low back pain.

OBJECTIVE: To describe the clinical management with spinal manipulation of a male patient with risk factors for lumbar disk herniation initially suffering from what appeared to be mechanical low back pain that evolved into radiculopathy; also to review issues pertinent to chiropractic/manipulative management of disk herniation. CLINICAL FEATURES: The patient initially suffered from unilateral low back pain and nonradicular/nonlancinating referral to the ipsilateral lower extremity. INTERVENTION AND OUTCOME: Disk herniation-in-evolution was included in the differential diagnosis, which was discussed with the patient, who then gave verbal informed consent for manipulative management. A day or so after the initial manipulation the presentation evolved to include S1 radiculopathy. Computed tomography, just after onset of radiculopathy, confirmed the clinical diagnosis of lumbosacral disk herniation. The patient continued with manipulative management and repeat computed tomography examination after clinical resolution about 2 months later revealed reduction in size of the apparently clinically significant herniation. CONCLUSION: Risk factors for the development of disk herniation should be considered when assessing patients suffering from what appears to be mechanical low back pain. The role played by manipulation in the development of disk herniation in this case was believed to be circumstantial rather than causal. Manipulation was used in the treatment of this patient over a period of approximately 2 months; after this time, clinical and partial computed tomography imaging resolution was evident. Ongoing clinical (neurologic) evaluation of patients with manifest or suspected disk herniation is an important aspect of management. Good-quality trials of manipulation for patients with disk herniation are imperative for the chiropractic profession.     

Conservative management of lumbar disk herniation

Treatment of lumbar disk herniation must be tailored to the individual patient. Bed rest, physical therapy, comfortable positioning, manipulation, drug therapy, and if necessary, hospitalization all have a place in the treatment of the acute phase. A surgical decision should be made only after thorough discussion with the patient. In patients with chronic or recurrent disk herniation, the prognosis for recovery from pain or dysfunction is often poor. Bed rest (if never tried before), physical therapy, biofeedback, stress management, rehabilitation programs, and drug therapy may be useful in alleviating discomfort and disability. Percutaneous diskectomy, while too new for accurate assessment, shows promise as a significant alternative to traditional lumbar laminectomy.     

Recurrence of radicular pain or back pain after nonsurgical treatment of symptomatic lumbar disk herniation

Suri P, Rainville J, Hunter DJ, Li L, Katz JN. Recurrence of radicular pain or back pain after nonsurgical treatment of symptomatic lumbar disk herniation.ObjectivesTo determine recurrence rates of lower-extremity radicular pain after nonsurgical treatment of acute symptomatic lumbar disk herniation (LDH), and to identify predictors of recurrence.DesignProspective inception cohort.SettingOutpatient spine clinic.ParticipantsPatients (N=79) reporting resolution of radicular pain after magnetic resonance imaging confirmation of LDH.InterventionsIndividualized nonsurgical treatment tailored to the patient. All patients received education, but other treatments varied depending on the individual.Main Outcome MeasuresResolution of radicular pain was defined as a pain-free period of ≥1 month. Patients who reported resolution of radicular pain within 1 year after seeking care for acute LDH were asked whether pain had recurred at 1 year after seeking care and were also reassessed 1 year after the time of resolution of radicular pain and 2 years after seeking care. Patients reported on recurrence and the date of recurrence, if any. We evaluated the 1-year incidence of recurrence, using Kaplan-Meier survival plots. We examined predictors of recurrence using bivariate and multivariate Cox proportional hazards models. We examined the secondary outcome of back pain recurrence using identical methods.ResultsTwenty-five percent (95% confidence interval [CI], 15–35) of individuals with resolution of radicular pain for at least 1 month reported subsequent recurrence of pain within 1 year after resolution. The only factor independently associated with radicular pain recurrence was the number of months prior to resolution of pain (hazard ratio per month=1.24; 95% CI, 1.13–1.37; P<.001). The 1-year incidence of back pain recurrence was 43% (95% CI, 30–56), and older age decreased the hazard of recurrence.ConclusionsRecurrence of radicular pain is relatively common after nonsurgical treatment of LDH and is predicted by longer time to initial resolution of pain.     

Spinal noradrenergic activation mediates allodynia reduction from an allosteric adenosine modulator in a rat model of neuropathic pain

Activation of adenosine A1 receptors by endogenous adenosine or synthetic agonists produces anti-nociception in animal models of acute pain and also reduces hypersensitivity in models of inflammatory and nerve-injury pain. Allosteric adenosine modulators facilitate adenosine agonist binding to the A1 receptor. The purpose of the current study was to examine the effect, mechanisms of action, and interaction with noradrenergic systems of intrathecal (i.t.) or oral administration of the allosteric adenosine modulator T62 in a rat model of neuropathic pain. A spinal nerve ligation rat model (SNL; ligation of left L5 and L6 spinal nerve roots) was used. One week after SNL surgery, an i.t. catheter was inserted. Withdrawal threshold to mechanical stimulation of the left hind paw was determined before and after surgery, confirming mechanical hypersensitivity. Oral or i.t. T62 reduced hypersensitivity induced by SNL. The effects of i.t. T62 were inhibited by i.t. injection of an A1 receptor antagonist and by an 2-adrenergic antagonist but not by an A2 adenosine receptor antagonist. Anti-dopamine hydroxylase (DH)-saporin treatment reduce spinal norepinephrine content by 97%, accompanied by an almost complete loss of DH immunoreactive axons in the spinal dorsal horn and neurons in the locus coeruleus. The effect of T62 was completely lost in animals treated with anti-DH-saporin. These data support the hypothesis that activation of the A1 receptor by the allosteric modulator, T62, produces anti-nociception via spinal noradrenergic activation.     

P2X3 receptor mediates heat hyperalgesia in a rat model of trigeminal neuropathic pain.

The present study was undertaken to determine the role of P2X3 receptor (P2X3R) on heat hyperalgesia in a newly developed rat model of trigeminal neuropathic pain. The unilateral infraorbital nerve (IoN) was partially ligated by 6-0 silk. To assess heat sensitivity, a vibrissal pad (VP) was placed on a hot plate and the latency until the rats withdrew their head was measured. Mechanical sensitivity of VP was also assessed by the use of von Frey filament. Both heat and mechanical hyperalgesia were observed at the VP ipsilateral to the IoN ligation. The latency to heat stimuli was prolonged after subcutaneous administration of pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, P2X1,2,3,5,7,1/5,2/3R antagonist) and 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate (TNP-ATP, P2X1,3,2/3,1/5R antagonist). The latency was shortened after administration of alpha,beta-methylene ATP (alpha,beta-meATP, P2X1,3,2/3R agonist), although no changes appeared after administration of beta,gamma-methylene-L-ATP (beta,gamma-me-L-ATP, P2X1R agonist). The protein gene product-9.5 and calcitonin gene-related peptide immunoreactive nerve fibers significantly decreased in the VP skin of ipsilateral to the IoN ligation. In the ipsilateral trigeminal ganglion, the number of P2X3-immunoreactive neurons significantly increased in the small cell group. In this study, we developed an experimental model of trigeminal neuropathic pain by partial ligation of IoN, which produced heat and mechanical hyperalgesia in the VP. Pharmacological and immunohistochemical studies revealed that the P2X3R plays an important role in the heat hyperalgesia observed in this model. PERSPECTIVE: The study describes the development of a novel model of trigeminal neuropathic pain. Heat hyperalgesia in this model was inhibited by peripheral injection of P2XR antagonists. The results suggest that P2X3R is a potential target for development of a novel therapy for trigeminal neuropathic pain.     

腰椎间盘突出症的影像学诊断研究现状

腰椎间盘突出症是纤维环破裂后髓核组织压迫腰骶脊神经根造成腰腿痛为主要临床表现的疾病,是目前骨科常见的疾病之一,其诊断主要依靠临床体征与影像学诊断。本文阐述了目前临床上常用或较前沿的影像学技术在腰椎间盘突出症诊断中的应用价值以及其相应的优缺点,分析了影像学检查在腰椎间盘突出症诊断中的发展趋势。     

老年腰椎间盘突出症的临床特点与手术治疗体会

目的探讨老年腰椎间盘突出症的临床特点和手术效果。方法对24例60岁以上腰椎间盘手术患者的临床资料进行回顾性分析。手术方法采用单侧或双侧扩大开窗、扩大神经根出孔术17例，半椎板切除术4例，全椎板切除术3例。结果24例随访平均2．4年，有效率为91．7％。但60～69岁年龄组与70岁以上年龄组相比，后者疗效有所下降（P〈0．01）。结论老年腰椎间盘突出症的发病特征是高位间隙和多节段病变比例增加，建议对非手术治疗无效的老年患者应积极手术治疗。     

冯氏脊柱定点旋转复位法治疗外伤致青少年腰椎间盘突出症的效果观察与护理

目的探讨青少年腰椎间盘突出症的发病原因,观察手法治疗和针对性护理的有效性。方法选取2000--2007年本科室收治的120例外伤致腰椎间盘突出症患者为研究对象,采用冯氏脊柱定点旋转复位法进行治疗,同时对其采用针对性护理模式进行护理,后对结果进行观察研究。结果经治疗护理后,120例患者中痊愈106例,好转12例,无效2例,总有效率达到98．3％。结论采用冯氏脊柱定点旋转复位法结合针对性护理对于外伤致青少年腰椎间盘突出症效果较好,值得临床推广应用。     

腰骶灵活性训练对腰椎间盘突出症患者干预效果的临床研究

目的观察腰骶灵活性训练对于腰椎间盘突出症患者活动度、疼痛和功能障碍的影响。方法前瞻性选取空军特色医学中心收治的腰椎间盘突出症患者51例,按照随机分组方法分为实验组(n=27)和对照组(n=24),两组患者均接受以冯氏脊柱定点旋转复位法为主的保守治疗,试验组患者在此基础上增加腰骶灵活性训练,即改良的腰骶猫式动作、仰卧位骨盆前后倾、骨盆侧屈、骨盆侧旋共4个动作,15个/组,2组/d,5 d/周,为期3周。在干预前后比较两组患者的坐位活动度、站位活动度、腰椎延展性以及主观疼痛(VAS评分)和功能障碍程度(ODI指数)。结果相比于对照组,实验组患者站立位腰椎屈曲延展性显著改善,差异具有统计学意义(t=2.557,P=0.014);站立位屈曲活动度(t=-3.035,P=0.004)、屈曲+右侧屈+右侧旋(t=-3.345,P=0.002)以及屈曲+左侧屈+左侧旋(t=-4.072,P=0.000)活动度均增加;VAS评分(t=2.908,P=0.008)和ODI指数(t=2.095,P=0.047)均显著减小,差异均有统计学意义(P<0.05)。结论腰骶灵活性训练能够改善腰椎间盘突出症患者腰椎的延展性,增加腰椎的活动度,改善腰椎-骨盆节律,改善前屈及前屈对角线动作的功能动作能力,并能够帮助腰椎间盘突出症患者缓解疼痛和主观功能障碍程度。     

Thoracic disk herniation presenting as abdominal and pelvic pain: a case report

We report the case of a young woman who presented with a 2-month history of severe abdominal and pelvic pain. The past history was significant for a fall from a bicycle 1 week before the onset of her pain. Physical examination was remarkable for periumbilical tenderness. Work-up including pelvic sonogram and diagnostic laparoscopy suggested endomyometritis. The pain was minimally relieved by nonsteroidal anti-inflammatory drugs and narcotic analgesics. Thoracic spine magnetic resonance imaging (MRI) revealed a large disk herniation at the T9-10 level compressing the spinal cord. The patient subsequently underwent T9-10 diskectomy and laminectomy with dramatic relief of her symptoms. Postoperative rehabilitation hastened her functional improvement. This is a rare case of symptomatic thoracic disk herniation after trauma presenting as abdominal and pelvic pain. Physicians should be aware of this unusual presentation of thoracic disk herniation to avoid invasive diagnostic procedures.     

Chiropractic rehabilitation of a patient with S1 radiculopathy associated with a large lumbar disk herniation

OBJECTIVE: To describe the nonsurgical treatment of acute S1 radiculopathy from a large (12 x 12 x 13 mm) L5-S1 disk herniation. CLINICAL FEATURES: A 31-year-old man presented with severe lower back pain and pain, paresthesia, and plantar flexion weakness of the left leg. His symptoms began 5 days before the initial visit and progressed despite nonsteroidal anti-inflammatory drugs and analgesic medication. An absent left Achilles reflex, left S1 dermatome hypesthesia, and left gastrocnemius/soleus weakness was noted. Magnetic resonance imaging demonstrated a large L5-S1 disk herniation. INTERVENTION AND OUTCOME: Initial treatment of this patient included McKenzie protocol press-ups to reduce and centralize symptoms, nonloading exercise for cardiovascular fitness, and lower leg isotonic exercises to prevent atrophy. Counseling was provided to reduce abnormal illness behavior risk. Later, flexion distraction and side-posture manipulation were provided to improve joint function. Sensory motor training, trunk stabilization exercises, and trigger point therapy were also used. He returned to modified work 27 days after symptom onset. A follow-up, comparative magnetic resonance imaging (MRI) study was unchanged. He was discharged as symptomatic (zero rating on both the Oswestry and numerical pain scales) after 50 days and 20 visits, although the left S1 reflex remained absent. Reassessment 169 days later revealed neither significant symptoms nor lifestyle restrictions. CONCLUSION: This case demonstrates the potential benefit of a chiropractic rehabilitation strategy by use of multimodal therapy for lumbar radiculopathy associated with disk herniation.     

COX2 in CNS neural cells mediates mechanical inflammatory pain hypersensitivity in mice

A cardinal feature of peripheral inflammation is pain. The most common way of managing inflammatory pain is to use nonsteroidal antiinflammatory agents (NSAIDs) that reduce prostanoid production, for example, selective inhibitors of COX2. Prostaglandins produced after induction of COX2 in immune cells in inflamed tissue contribute both to the inflammation itself and to pain hypersensitivity, acting on peripheral terminals of nociceptors. COX2 is also induced after peripheral inflammation in neurons in the CNS, where it aids in developing a central component of inflammatory pain hypersensitivity by increasing neuronal excitation and reducing inhibition. We engineered mice with conditional deletion of Cox2 in neurons and glial cells to determine the relative contribution of peripheral and central COX2 to inflammatory pain hypersensitivity. In these mice, basal nociceptive pain was unchanged, as was the extent of peripheral inflammation, inflammatory thermal pain hypersensitivity, and fever induced by lipopolysaccharide. By contrast, peripheral inflammation–induced COX2 expression in the spinal cord was reduced, and mechanical hypersensitivity after both peripheral soft tissue and periarticular inflammation was abolished. Mechanical pain is a major symptom of most inflammatory conditions, such as postoperative pain and arthritis, and induction of COX2 in neural cells in the CNS seems to contribute to this.     

Spinal administration of a delta opioid receptor agonist attenuates hyperalgesia and allodynia in a rat model of neuropathic pain.

Neuropathic (NP) pain is a debilitating chronic pain disorder considered by some to be inherently resistant to therapy with traditional analgesics. Indeed, micro opioid receptor (OR) agonists show reduced therapeutic benefit and their long term use is hindered by the high incidence of adverse effects. However, pharmacological and physiological evidence increasingly suggests a role for deltaOR agonists in modulating NP pain symptoms. In this study, we examined the antihyperalgesic and antiallodynic effects of the spinally administered deltaOR agonist, d-[Ala(2), Glu(4)]deltorphin II (deltorphin II), as well as the changes in deltaOR expression, in rats following chronic constriction injury (CCI) of the sciatic nerve. Rats with CCI exhibited cold hyperalgesia and mechanical allodynia over a 14-day testing period. Intrathecal administration of deltorphin II reversed cold hyperalgesia on day 14 and dose-dependently attenuated mechanical allodynia. The effects of deltorphin II were mediated via activation of the deltaOR as the effect was antagonized by co-treatment with the delta-selective antagonist, naltrindole. Western blotting experiments revealed no changes in deltaOR protein in the dorsal spinal cord following CCI. Taken together, these data demonstrate the antihyperalgesic and antiallodynic effectiveness of a spinally administered deltaOR agonist following peripheral nerve injury and support further investigation of deltaORs as potential therapeutic targets in the treatment of NP pain.     

临床护理路径在腰椎间盘突出症射频热凝消融术中的应用

目的：探讨临床护理路径在腰椎间盘突出症射频热凝术护理中的临床效果。方法将2012年10月至2013年3月在本科接受腰椎间盘突出症射频热凝消融术的患者50例作为对照组,实施常规护理及健康教育;将2013年4月至9月50例患者作为观察组,依据临床护理路径方法及内容实施护理及健康教育。对实施临床护理路径前后2组患者平均手术耗时、术中术后并发症、住院天数、住院费用、护理工作满意率进行比较。结果2组患者平均手术耗时、住院天数、住院费用、手术并发症、健康教育知晓率、对护理工作满意率,观察组均显著优于对照组,差异有统计学意义( P<0.05)。结论临床护理路径在腰椎间盘突出症射频热凝消融术护理中的应用,不仅可以减少围手术期并发症、缩短手术用时及住院日、降低住院费用,还可以提高患者健康教育知晓率及对护理工作满意率。