Clinical features of neck and shoulder pain (Katakori) in Japanese hospital workers.

BACKGROUND: Non-specific pain or discomfort in the neck and shoulder girdle, called katakori in Japanese, is a common, chronic musculoskeletal condition worldwide. However, its various clinical features are incompletely characterized, even among medical professionals. We aimed to clarify factors affecting katakori and to investigate objectively the associated neck muscle stiffness and skeletal muscle volume. METHODS: All staff members at our private hospital were surveyed about their lifestyle, physical and mental status, and katakori symptoms, using a self-administered questionnaire. Multiple logistic regression analysis was used to explore possible katakori risk factors. On secondary assessment, ultrasound elastography of the trapezius muscle as well as limb/trunk muscle mass were compared between subjects with severe symptoms and subjects without katakori, using propensity score matching. RESULTS: Of 359 participants enrolled, nearly 75% had katakori to some degree. Spending time on a computer during work (adjusted odds ratio [aOR]:1.82 for 3-6 hours, aOR:2.48 for > 6 hours), being female (aOR:3.75), and having unsatisfactory sleep (aOR:2.92) were potential risk factors for katakori. Comparison of 13 matched pairs showed a significantly stiffer trapezius in subjects with severe katakori symptoms, but no apparent differences in limb/trunk muscle mass. CONCLUSIONS: Katakori was particularly prevalent in our hospital staff. Possible risk factors for disabling katakori were doing long-term computer work, being female, and having unsatisfactory sleep. Symptoms seem to be associated with elevated neck muscle stiffness. These findings could guide working condition improvements to mitigate katakori.

Reduction in anxiety during treatment with exercise and duloxetine is related to improvement of low back pain-related disability in patients with non-specific chronic low back pain.

BACKGROUND: Non-invasive treatment is generally recommended for patients with non-specific chronic low back pain (CLBP). However, the impact of combination therapy with physical exercise and a serotonin-norepinephrine reuptake inhibitor has not been clarified in patients with non-specific CLBP. This study assessed the efficacy of combination treatment with exercise and duloxetine on non-specific CLBP and aimed to identify factors that contributed to improvement of LBP-induced disability. METHODS: This prospective study was conducted on consecutive outpatients with non-specific CLBP. Patients received a supervised home-based exercise program and duloxetine administration for 15 weeks. The Roland-Morris Disability Questionnaire (RDQ), Numerical Rating Scale (NRS), Hospital Anxiety and Depression Scale (HADS), and Pain Catastrophizing Scale (PCS) were assessed at baseline and 15 weeks. Multiple logistic regression modeling was used to identify factors associated with an improvement in RDQ. RESULTS: Forty-two patients were enrolled. Overall, scores on the RDQ, NRS, and PCS (total score, magnification, helplessness) were significantly reduced at 15 weeks (p < 0.01 for all). An improvement of disability was confirmed in 22 patients (52%). A higher HADS depression score before and after the intervention was significantly associated with a lack of improvement in disability (p < 0.01). Further, a reduction in HADS anxiety score over 15 weeks was a significant factor associated with an improvement in disability (odds ratio:1.99;95% CI:1.26-3.65). CONCLUSIONS: Supervised exercise plus duloxetine resulted in favorable outcomes and an improvement of LBP-related disability in approximately 50% of patients. A reduction in anxiety over treatment was associated with the improved disability.

Comparisons between the efficacy of limaprost alfadex and pregabalin in cervical spondylotic radiculopathy : design of a randomized controlled trial.

BACKGROUND: Cervical spondylotic radiculopathy (CSR) is a relatively common neurological disease caused by the mechanical compression of nerve roots. Limaprost, a prostaglandin E1 derivative, functions as a vasodilator and has been used in the treatment of lumbar spinal stenosis in Japan. However, the effects of limaprost in cervical radiculopathy remain unclear. Our aim was to compare the efficacy of limaprost with that of pregabalin, which is widely used for the treatment of neuropathic pain. METHODS: In this randomized trial, patients with CSR received either limaprost or pregabalin orally for 8 weeks, along with nonsteroidal anti-inflammatory drugs. The primary outcomes were assessed using a numerical rating scale of pain and numbness, both at rest and during movement. Secondary outcomes were assessed using Short Form-36, provocation tests, painDETECT questionnaire, and subjective global assessment. The obtained data were evaluated according to the per-protocol analysis principle. RESULTS: A total of 46 patients were enrolled in this study, and 35 were available for analysis. A greater reduction in pain score was observed in neck pain during movement, and scapular and arm pain both at rest and during movement in the pregabalin-treated group up to 4 weeks. In the limaprost-treated group, numbness of the arm during movement showed a marked alleviation compared to the pregabalin-treated group at 8 weeks. There were no apparent differences between the two groups in terms of the secondary outcomes. CONCLUSIONS: Although pregabalin provided an earlier pain relief than limaprost, limaprost was superior to pregabalin in treating arm numbness. Limaprost might be one of the effective therapeutic options for CSR in primary care settings.

Prospective one-year follow-up of lumbar spinal stenosis in a regional community.

PURPOSE: Lumbar spinal stenosis (LSS) is a common condition in the aging population. However, limited information exists on discrepancies between LSS symptoms and imaging findings and/or prognostic factors of LSS, as well as the relationship between changes in LSS symptoms and quality of life (QoL) during the natural course of LSS. The purpose of the current study was to clarify any changes in clinically diagnosed LSS at a one-year follow-up, and identify its prognostic factors, using a community-dwelling cohort. PARTICIPANTS AND METHODS: In this study, the presence of LSS, its associated comorbidities, and the status of QoL pertaining to general health and low-back pain were assessed in 1,080 community-dwelling volunteers. The same assessment was carried out a year after the initial survey. Clinically diagnosis as LSS (LSS-positive) was determined by a validated diagnostic support tool in the form of a self-administered, self-reported history questionnaire. QoL was assessed using the 36-Item Short Form Health Survey and the Roland-Morris Disability Questionnaire. RESULTS: Among subjects who were LSS-positive in the initial assessment, 54% were clinically diagnosed as negative for LSS (LSS-negative) after the one-year period, whereas 10% of those who were initially diagnosed as LSS-negative changed to LSS-positive during the same period. With the improvement or deterioration of LSS-positive/negative status, low-back pain-related QoL and some components of the 36-Item Short Form Health Survey similarly improved or deteriorated. Decisive prognostic factors of LSS-positive status were not determined at the one-year follow-up. CONCLUSION: Approximately half of the subjects who had initially been diagnosed as LSS-positive converted to LSS-negative after one year. Prognostic factors of LSS-positive diagnosis after one-year follow-up were not detected.

Comparison of the effects of treatment with celecoxib, loxoprofen, and acetaminophen on postoperative acute pain after arthroscopic knee surgery: A randomized, parallel-group trial.

BACKGROUND: Selective cyclooxygenase-2 (COX-2) inhibitors, conventional non-selective nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen have been adopted for the relief of mild to moderate acute and chronic pain. However, it remains unclarified whether the therapeutic differences in pain sensation exist among these agents. The aim of this study was to compare the efficacy of different types of analgesic agents for postoperative acute pain management. METHODS: A single-center, randomized, controlled study was performed in consecutive patients who underwent the second-look procedure with removal of internal fixation after anterior cruciate ligament reconstruction or arthroscopic meniscal repair/meniscectomy. Celecoxib (400 mg for the first dose and then 200 mg), loxoprofen (60 mg), or acetaminophen (600 mg) was orally administered from postoperative 3 h. The pain intensity on a 100-mm VAS scale and subjective assessment of therapeutic pain-relief were compared among these three treatment groups until postoperative 2 days. The acquired data were analyzed according to the per-protocol analysis principle. RESULTS: A total of 432 patients were screened, and 160 were enrolled. The VAS score tended to decrease over time in all groups. There was a significant improvement in the pain score both at rest and on movement, and subjective impression in the celecoxib-treated group compared with acetaminophen at postoperative 2 days. On the other hand, loxoprofen resulted in the benefit only in the pain score at rest in comparison with acetaminophen. Any comparisons between celecoxib and loxoprofen showed insignificant differences throughout observations. No adverse effects were confirmed in each group. CONCLUSIONS: These obtained findings in our dose setting conditions suggest that celecoxib and loxoprofen treatments were superior to acetaminophen in pain-relief, though the superiority of loxoprofen over acetaminophen was modest. Overall, selective COX-2 inhibitors including conventional NSAIDs seem to have a possible advantage in acute pain management of relatively less invasive surgery.

Limaprost alfadex and nonsteroidal anti-inflammatory drugs for sciatica due to lumbar spinal stenosis.

PURPOSE: Limaprost, a prostaglandin E1 analog, has vasodilatory properties and increases blood flow of the nerve root. However, it has not been clarified whether limaprost affects pain sensation associated with radiculopathy due to lumbar spinal stenosis (LSS). The aim of this study was to compare the efficacy of oral limaprost with nonsteroidal anti-inflammatory drugs (NSAIDs) for radiculopathy. METHODS: We performed a multicenter prospective randomized trial. Patients with LSS who had radicular-type neurologic intermittent claudication assessed based on a self-reported diagnostic support tool were randomized into three treatment groups. Limaprost, NSAIDs, or limaprost plus NSAIDs were administered orally for 6 weeks. Leg pain, low back pain (LBP) and the associated symptoms were assessed by a numerical rating scale (NRS) both at rest and on movement as well as the Roland-Morris Disability Questionnaire (RDQ) and Short Form (SF)-36. RESULTS: Sixty-one patients were enrolled in the study. Each treatment finally reduced radicular pain, and the improvement was prominent in a combination treatment. There were no significant differences in radicular pain among three groups at final follow-up. LBP was not influenced by limaprost, and a significant reduction of LBP and RDQ was confirmed in a combination treatment compared with limaprost. Physical function of the SF-36 subscales after a combination treatment showed a marked alleviation compared with NSAIDs. CONCLUSIONS: These obtained findings suggest that the effects of limaprost seem to be limited to radicular pain, not for LBP. Overall, a combination treatment might be more effective in the management of radiculopathy induced by LSS than monotherapy with either agent.

Demographic characteristics of 3,659 Japanese patients with obstructive sleep apnea-hypopnea syndrome diagnosed by full polysomnography: associations with apnea-hypopnea index.

Information on obstructive sleep apnea-hypopnea syndrome (OSAHS) in Japan has been limited. The purposes of this clinical study were to evaluate the demographic characteristics of Japanese OSAHS patients and to assess how demographic factors are associated with OSAHS severity. We analyzed 3,659 OSAHS patients who underwent polysomnographic evaluation between January 2000 and December 2004 at 11 hospitals in Niigata Prefecture, Japan. Data consisted of apnea-hypopnea index (AHI) and demographic characteristics, including sex, age, and body-mass index, for statistical analysis. Levels of obesity were classified according to the WHO criteria. The male-to-female patient ratio for OSAHS was 4.6, and male patients presented more severe OSAHS than female patients. High AHI and a high proportion of moderate to serious OSAHS (AHI > or = 15) were found among the patients in their 30s, as well as female patients in their 70s and male patients in their 80s. The AHI and the proportion of moderate-to-serious OSAHS (AHI > or = 15) were greater in patients classified as underweight than in normal weight patients. In conclusion, there is a higher male predominance in the prevalence of OSAHS, and in both sexes, the results suggest different pathophysiological mechanisms of deteriorating OSAHS between adults under age 55 and adults 55 years or over. In addition, underweight patients exhibit more severe OSAHS than normal weight patients.

Mid-term and long-term follow-up data after placement of the Graf stabilization system for lumbar degenerative disorders.

OBJECT: The Graf pedicle screw and ligament device is designed to provide flexible stabilization to prevent abnormal spinal movement. The purpose of this study was to investigate radiographic and clinical outcomes during a minimal 5-year follow-up period. METHODS: Between 1991 and 1997, 43 consecutive patients (whose mean age was 61 years) with lumbar degenerative disease underwent decompression and stabilization in which the Graf system was placed. Data were available for 31 patients who attended follow up for the minimal 5-year period. In a retrospective review, the authors assessed measurements on radiographs, clinical results (using Japanese Orthopaedic Association [JOA] Scale scores), and low-back pain (using a visual analog scale [VAS] score), preoperatively and postoperatively at 1, 3, 5, and/or 10 years. Radiographic measurements included sagittal and frontal range of motion (ROM), regional lordosis, and posterior disc height as well as the extent of degenerative spondylolisthesis. Final follow-up JOA and VAS scores were significantly better than preoperative scores. Sagittal and frontal ROM was significantly reduced at 1 and 5 years, respectively, compared with preoperative values, and a gradual reduction persisted throughout the follow-up period. Compared with its preoperative status, the disc height ratio (adjacent segments to the operated level) was reduced 5 years after surgery. A significant inhibition of the vertebral slippage was detected only in the flexion position. CONCLUSIONS: Analysis of these data indicated that the Graf system eventually leads to successful fusion, suggesting the presence of stability in all three dimensions. The use of the Graf system should continue to be evaluated as an alternative device in the treatment of lumbar degenerative disease.

Changes in pain behavior and histologic changes caused by application of tumor necrosis factor-alpha to the dorsal root ganglion in rats.

STUDY DESIGN: Histologic changes in the dorsal root ganglion (DRG) and the nociceptive stimulation thresholds were studied in rats. OBJECTIVE: To examine the effects of tumor necrosis factor-alpha (TNF) with special reference to pain behavior and histology of the DRG. SUMMARY OF BACKGROUND DATA: Recently, it was reported that local application of nucleus pulposus induces a characteristic tissue reaction at the surface of the DRG. However, to our knowledge, there have been no previous reports about the relationship between the histologic changes and pain behavior caused by cytokines. METHODS: Recombinant TNF was applied to the L4 DRG. Mechanical and thermal nociceptive thresholds were tested. The L4 DRG was sectioned and observed by light microscopy. RESULTS: After the application of 5 ng/microL TNF, significant differences were observed in mechanical and thermal stimulation thresholds. At the site of application of TNF, a characteristic a semilunar-shaped enlargement was observed. The average width of the part was significantly larger in the 5 ng/microL TNF application, as compared to the 0.5-ng/microL TNF application. CONCLUSIONS: The higher concentration of TNF used induced allodynia and hyperalgesia responses. Because the region showing the histologic changes was significantly larger after application of the higher concentration of TNF, the reaction of the DRG may be related to pain.

Nerve growth factor content in dorsal root ganglion as related to changes in pain behavior in a rat model of experimental lumbar disc herniation.

STUDY DESIGN: The time courses of nerve growth factor content and pain-related behavior were examined using experimental disc herniation models. OBJECTIVES: To investigate a relationship between nerve growth factor level and pain behavior. SUMMARY OF BACKGROUND DATA: An induction of nerve growth factor in the periphery is regarded as a major contributor of inflammatory hyperalgesia and neuropathic pain. However, it has not been clarified quantitatively whether disc herniation induces changes in nerve growth factor levels in the dorsal root ganglion in relation to pain-related behavior. METHODS: A total of 140 rats were used in this study. The animals had their left L4 nerve roots and associated dorsal root ganglion exposed and were equally divided into 4 groups: L4-L5 disc puncture, displacement of L4 nerve roots/dorsal root ganglion, the combination of disc puncture and displacement, and sham exposure. The content of nerve growth factor in the affected dorsal root ganglion was assessed by enzyme-linked immunosorbent assay as well as pain behavior during a postoperative 21-day period. RESULTS: Disc puncture resulted in nerve growth factor induction at postoperative day 3, but not apparent behavioral changes. Mechanical displacement induced nerve growth factor at postoperative day 1 and mechanical allodynia at postoperative day 3, respectively (P < 0.05). In the combination model, there were more pronounced changes in nerve growth factor induction and both mechanical and thermal threshold during 7 days after surgery (P < 0.05). CONCLUSIONS: These data suggest the possibilities that elevated nerve growth factor level is partly involved in pain behavior and further the combined model mimicking the clinical situation, which causes the marked neuronal responses, is helpful to advance the understanding of the mechanisms underlying sciatica due to lumbar disc herniation.

Lumbar sympathectomy increases blood flow in a dog model of chronic cauda equina compression.

OBJECTIVE: This study was designed to assess changes in blood flow of the dog cauda equina after lumbar sympathectomy using an experimental chronic cauda compression model. METHODS: The cauda equina was compressed at 10 mm Hg with a plastic balloon in all animals (n = 12). One week later, bilateral lumbar sympathectomy was carried out in the LSX group (n = 7), and vessels of the cauda equina were thereafter observed for 90 minutes using a specially designed microscope supplied with a video camera. Five animals did not undergo sympathectomy and were used as controls. The volume of blood flow was calculated from two parameters: velocity (mm/s) and diameter (microm) of a vessel observed in each animal. RESULTS: The increment in vessel diameter in the LSX group was pronounced at 30 and 45 minutes after sympathectomy compared with the control group (P < 0.05). Blood flow in the LSX group was increased at 30 minutes depending on dilation of the vessel diameter compared with the control group (P < 0.05). The velocity in the observed vessels remained unchanged throughout the measurements. CONCLUSIONS: These data suggest that lumbar sympathectomy could induce an increase in blood flow of the compressed cauda equina. As lumbar sympathetic block increases blood flow not only in the lower limbs but also in the cauda equina, it might be evaluated for a conservative treatment of intermittent claudication due to lumbar spinal canal stenosis.

Selective inhibition of tumor necrosis factor-alpha prevents nucleus pulposus-induced histologic changes in the dorsal root ganglion.

STUDY DESIGN: The possibility to prevent nucleus pulposus-induced structural changes of the dorsal root ganglion (DRG) by selective tumor necrosis factor-alpha (TNF-alpha) inhibition was assessed in an experimental model in the rat spine. OBJECTIVES: To evaluate the role of TNF-alpha in the mediation of nucleus pulposus-induced structural changes by using selective inhibition and to confirm the effect of TNF-alpha inhibitor at the point of histologic findings. SUMMARY OF BACKGROUND DATA: TNF-alpha is known to be released from the nucleus pulposus, and has been suggested to play a key role in chemical damage of the adjacent nerve tissue. The TNF-alpha inhibitor prevents the reduction of nerve conduction velocity and may limit the nerve fiber injury, intracapillary thrombus formation, and intraneural edema formation caused by nucleus pulposus. However, there is no report on the effect of the inhibitor regarding histologic findings and the appearance of the TNF-alpha in the DRG exposed to nucleus pulposus. METHODS: 1) Rats were treated with an intraperitoneal injection of infliximab. Nucleus pulposus from the disc was obtained 1, 3, 7, 14, and 21 days after the injection. The TNF-alpha-positive cells were observed using immunohistochemistry. 2) Disc herniation of the nucleus pulposus was made on the L4-L5 disc in rats. Two groups were treated with selective TNF-alpha inhibitor 1 day before or 3 hours after surgery. The other group received no TNF-alpha inhibitor. The L4 DRG was resected 1, 3, 7, 14, and 21 days after surgery. The specimens were processed for hematoxylin and eosin staining and immunohistochemistry using rabbit antisera to TNF-alpha. The histologic findings and TNF-alpha-positive cells were observed by light microscopy. RESULTS: 1) While positively stained immunoreactive TNF-alpha appeared between 7 and 21 days, no immunoreactive TNF-alpha was observed 1 and 3 days after injection in the nucleus pulposus. 2) The histologic changes of the DRG caused by nucleus pulposus were smaller in the infliximab treatment group than those in the nontreatment group. The number of immunoreactive TNF-alpha cells was high 1 and 3 days after surgery in the DRGs of disc herniation rats that were treated without an injection of the inhibitor, low on day 7 and 14, and very low on day 21 after surgery. No immunoreactive TNF-alpha was observed in the DRGs of the TNF-alpha inhibitor treatment groups on day 1, 3, and 21 after surgery. Weakly stained cells were sometimes observed in rats at day 7 and 14 after surgery. CONCLUSIONS: Infliximab may prevent the histologic damage induced by nucleus pulposus. When rats were given a single intraperitoneal injection of infliximab at the beginning of disc herniation, the histologic damage seemed to be reduced in comparison with the nontreated rats.

Infliximab attenuates immunoreactivity of brain-derived neurotrophic factor in a rat model of herniated nucleus pulposus.

STUDY DESIGN: The effect of infliximab, a chimeric monoclonal antibody to TNF-alpha, on induction of brain-derived neurotrophic factor (BDNF) was examined using an experimental herniated nucleus pulposus (NP) model. OBJECTIVES: To investigate whether treatment of infliximab could attenuate an induction of BDNF, which functions as a modulator of pain, following NP application to the nerve root. SUMMARY OF BACKGROUND DATA: Evidence from basic scientific studies proposes that TNF-alpha is involved in the development of NP-induced nerve injuries. However, the therapeutic mechanisms of infliximab against pain have not been elucidated experimentally. METHODS: Twenty rats were used in this study. In the test groups, the animals underwent application of NP to the L4 nerve roots and received a single systemic (intraperitoneal) injection of infliximab at the time of surgery (Infli-0 group, n = 5) or at 1 day after operation (Infli-1 group, n = 5). As a control treatment, sterile water was administered intraperitoneally to 5 rats with NP application (NP group) and to 5 sham-operated rats (sham group). On day 3 after surgery, the L4 dorsal root ganglion (DRG) and L4 spinal segment were harvested and assessed regarding BDNF immunoreactivity. RESULTS.: Application of NP induced a marked increase of BDNF immunoreactivity in number in the DRG neurons and within the superficial layer in the dorsal horn compared with the sham group (P < 0.01). Infliximab treatment in the Infli-0 and Infli-1 groups reduced the BDNF induction in both DRG and spinal cord (P < 0.05). CONCLUSION: These findings indicate that infliximab attenuates the elevated BDNF levels induced by NP. The present study therefore further indicates the importance of TNF-alpha in sciatica due to disc herniation and the possible therapeutic use of a TNF-alpha inhibitor for this condition.

Distribution and appearance of tumor necrosis factor-alpha in the dorsal root ganglion exposed to experimental disc herniation in rats.

STUDY DESIGN: Distribution and appearance of tumor necrosis factor-alpha (TNF-alpha) in the dorsal root ganglion (DRG) exposed to experimental disc herniation were investigated using an immunohistochemical method in rats. OBJECTIVES: To study the distribution and appearance of TNF-alpha in the DRG following experimental disc herniation in rats. SUMMARY OF BACKGROUND DATA: Nucleus pulposus in the epidural space induces spinal nerve root injury not only by mechanical but also chemical mechanisms. Cytokines may play a key role in the chemical damage. There is, however, no report on the distribution and appearance of TNF-alpha in the DRG exposed to nucleus pulposus. METHODS: Nucleus pulposus from the discs was smeared on the glass slides and processed for immunohistochemistry by the avidin-biotinylated peroxidase complex technique using rabbit antisera to TNF-alpha in rats. A herniation of the nucleus pulposus was made by incision of the L4-L5 disc in rats. The L4 and L5 DRGs were resected 1, 3, 7, 14, and 21 days after surgery. The specimens were processed for immunohistochemistry using rabbit antisera to TNF-alpha. The TNF-alpha-positive cells were observed and counted using light microscopy. Distribution of the TNF-alpha products was compared on each day after surgery. RESULTS: A positive staining was seen in the cell bodies and in the matrix between the cells in the smeared nucleus pulposus. In the L4 DRG sections, the number of positive cells was significantly higher in the disc incision group than in the sham group at 1, 3, 7, and 14 days after surgery (P < 0.05). The positive cells showed a decrease in number day by day after surgery. On the contrary, in the L5 DRG, only a few positive cells were observed in the disc incision group after surgery. There was no statistically significant difference between disc incision and the sham groups at each day after surgery for the L5 DRGs. CONCLUSIONS: The immunoreactivity of TNF-alpha in the DRG directly exposed to nucleus pulposus increases during 2 weeks. A collapse of the positive cells was seen in the DRG directly exposed to the nucleus pulposus.

Immunoreactivity of brain-derived neurotrophic factor in rat dorsal root ganglion and spinal cord dorsal horn following exposure to herniated nucleus pulposus.

The pain mechanisms underlying radiculopathy due to disc herniation are still incompletely understood. This study assessed changes in brain-derived neurotrophic factor (BDNF) expression, a modulator of nociceptive information, in the dorsal root ganglion (DRG) and spinal cord dorsal horn following experimental disc herniation. Immunohistochemical analysis revealed an increase in percentage of BDNF-immunoreactive (IR) neurons profiles in the affected DRG and marked elevation in the BDNF-IR regions within both the superficial and deep layers at the corresponding spinal level with a peak at 3 days after nucleus pulposus (NP) application. These results thus show that herniated NP increases the BDNF production in the pain-processing neurons. Such changes can contribute to the development of inflammatory hyperalgesia.

Effects of neutralizing antibodies to tumor necrosis factor-alpha on nucleus pulposus-induced abnormal nociresponses in rat dorsal horn neurons.

STUDY DESIGN: The effect of an anti-tumor necrosis factor alpha (anti-TNFalpha) antibody on abnormal discharges caused by application of nucleus pulposus to the nerve root was investigated in an electrophysiologic study. OBJECTIVES: To assess whether inhibition of TNFalpha can reduce nucleus pulposus-induced abnormal discharges. SUMMARY OF BACKGROUND DATA: It has been shown that TNFalpha, a proinflammatory cytokine, is a key pathogenic factor in the development of nucleus pulposus-induced abnormal discharges as a pain sensation. However, the electrophysiologic mechanisms involved in sciatica after disc herniation still have not been elucidated. METHODS: Extracellular activities of wide-dynamic-range neurons were assessed in 21 rats. Autologous nucleus pulposus harvested from the tail was applied to the L5 nerve root. The animals were simultaneously treated with antibodies to TNFalpha (anti-TNF + nucleus pulposus group) and with phosphate-buffered saline (nucleus pulposus group). As a control (control group), a similar volume of muscle was applied to the nerve root with phosphate-buffered saline. Responses of wide-dynamic-range neurons to noxious and innocuous stimuli were examined for 2 hours. RESULTS: Discharges evoked during noxious stimulation and discharges after withdrawal of stimulation in the nucleus pulposus group were significantly higher than those in the control group (P < 0.05). In the anti-TNF + nucleus pulposus group, discharges after withdrawal of stimulation were remarkably inhibited, as compared with those of the nucleus pulposus group (P < 0.05). However, evoked discharges during stimulation apparently were not inhibited. Responses to innocuous stimulation did not change throughout the measurements. CONCLUSIONS: These data indicate that application of TNFalpha antibodies to the nerve root partially prevents the nucleus pulposus-induced abnormal nociresponses. Therefore, anti-TNFalpha treatment may have a therapeutic effect on sciatica after lumbar disc herniation.

Exogenous tumor necrosis factor-alpha induces abnormal discharges in rat dorsal horn neurons.

STUDY DESIGN: An electrophysiologic study to examine effects of exogenous application of tumor necrosis factor-alpha (TNF-alpha ) activities and nociresponses of dorsal horn neurons in the spinal cord at L5. OBJECTIVES: To investigate the role of TNF-alpha in the induction and development of hyperalgesia in neural mechanisms responsible for a radicular pain. SUMMARY OF BACKGROUND DATA: TNF-alpha is found in the herniated disc and known to play a pivotal role in the development of inflammatory hyperalgesia; however, it is not known whether TNF-alpha causes abnormal discharge in the dorsal horn neurons and enhances nociresponse. METHODS: Single-unit activities of neurons in the L5 superficial dorsal horn were extracellularly recorded, using 28 urethane-anesthetized rats. The wide dynamic range and nociceptive-specific neurons activated by stimulation of the hind paw were selected. Effects of exogenous TNF-alpha were examined regarding 1) spontaneous discharges of wide dynamic range and nociceptive-specific neurons, 2) responses of wide dynamic range neurons to noxious stimulation, and 3) morphologic changes in the dorsal root ganglion. RESULTS: Application of TNF-alpha to the nerve root induced 1) a significant increase in spikes/sec in spontaneous discharges of wide dynamic range and nociceptive-specific neurons, 2) enhanced responses of wide dynamic range neurons to noxious stimulation, and 3) inflammatory changes in the ganglion. CONCLUSION: These results suggest the possibility that TNF-alpha produced in the vicinity of nerve roots due to disc herniation might cause ectopic discharges in primary afferent fibers and thereby induce the prolonged excitation in pain-processing neurons responsible for radicular pain.

Epidural application of nucleus pulposus enhances nociresponses of rat dorsal horn neurons.

STUDY DESIGN: An electrophysiologic study to examine responses of dorsal horn neurons in the rat L5 spinal cord to noxious stimuli after disc herniation or application of the nucleus pulposus to the L5 nerve root. OBJECTIVES: To investigate the pathogenic role of nucleus pulposus in the neural mechanism underlying sciatica and low back pain. SUMMARY OF BACKGROUND DATA: Application of the nucleus pulposus to the lumbar nerve root induced morphologic, vascular, and functional changes in the nerve root, suggesting that some factors in the nucleus pulposus may be implicated in the pathogenesis of chronic changes. However, it has not been studied whether the epidural application of nucleus pulposus enhances nociresponses of pain-processing neurons in the superficial dorsal horn of the spinal cord. METHODS: Extracellular recordings were made from the L5 dorsal horn neurons in 20 Wistar rats. The wide-dynamic-range (WDR) neurons activated by electric stimulation of the ipsilateral footpad of hindpaw were selected, and their responses to noxious and innocuous stimulation were examined after L5-L6 disc herniation onto the L5 nerve root (Group A) and application of the autologous nucleus pulposus (Group B) or fat tissues (Groups C and D). RESULTS: The herniation of the nucleus pulposus (Group A) and application of the autologous nucleus pulposus (Group B) to the nerve root remarkably enhanced responses of WDR neurons to noxious stimuli for hours, whereas application of fat tissue scarcely enhanced nociresponses (Groups C and D). CONCLUSIONS: Results suggest that somewhat pathogenic factors in the nucleus pulposus may have a crucial role in the induction of hyperalgesia. This may help to elucidate the reason why a severe pain is sometimes induced without a visually identified protrusion.