Activation of glial cells in the spinal cord of a model of lumbar radiculopathy

Purpose  

Glial cells in the spinal cord of a lumbar radiculopathy model were investigated using immunohistochemical methods. Neuropathic pain is a consequence of neural plasticity. In models of neuropathic pain models, roles for glial cells in the development of pain behaviors have been reported. Accumulating evidence suggests that activation of p38 mitogen-activated protein kinase (p38) in glial cells contributes to the pathogenesis of neuropathic pain. We examined whether activation of glial cells is involved in the development of neuropathic pain-like behavior observed in a model of lumbar radicular pain that we developed. However, the pathogenesis of lumbar radiculopathy and in particular the effect of spinal glial activation on pain transmission in the dorsal horn of the spinal cord are still not fully known.     

Pregabalin, celecoxib, and their combination for treatment of chronic low-back pain

Background  

The efficacy and safety of the association of celecoxib [a selective cyclooxygenase-2 (COX-2) inhibitor] and pregabalin (commonly used to control neuropathic pain), compared with monotherapy of each, were evaluated for the treatment of chronic low-back pain, a condition known to be due to neuropathic as well as nociceptive pain mechanisms.     

Activation of satellite cells in the dorsal root ganglia in a disc-punctured rat model

Background  

The neural mechanisms underlying discogenic low back pain caused by disc degeneration remain unclear. Previous studies demonstrated that satellite cells (SC) play an important role in neuropathic pain.     

Adenylate cyclase inhibition attenuates neuropathic pain but lacks pre-emptive effects in rats

Purpose

There is evidence that cyclic adenosine monophosphate (cAMP) transduction is involved in nociceptive processing. We previously showed that intrathecal injection of an adenylate cyclase inhibitor attenuated tactile allodynia caused by partial sciatic nerve ligation (PSNL) in rats. The present study investigates the pre-emptive effects of spinal cAMP transduction on nociceptive processing in a chronic neuropathic pain model.

Methods

Intrathecal catheterization and PSNL were performed in male Sprague-Dawley rats. Nociceptive responses to mechanical and thermal stimuli were evaluated at the hindpaw at 2 hr and at 3, 7, and 14 days after PSNL. The pre-emptive effects of the intrathecal adenylate cyclase inhibitor, SQ22536 (0.7 μmol · L^?1, 30 min before or after nerve ligation) were assessed. Also, the spatial and temporal expression profiles and immunoreactivity in the spinal cord of the cAMP response element binding protein (CREB) and its phosphorylated proteins (CREB-IR and p-CREB-IR) were analyzed.

Results

Compared with the rats treated with the vehicle, allodynia and hyperalgesia were significantly attenuated at 1–3 days by the intrathecal injection of SQ22536 performed either before or after ligation. The expression of CREB was significantly higher after ligation (P < 0.05), but differences were not observed between groups. Intrathecal injection of SQ22536, either before or after ligation, partially reduced p-CREB-IR protein expression in comparison with the vehicle control, especially after the first 3 days (P < 0.05).

Conclusion

Our results show a possible association between the increase in p-CREB and PSNL-induced neuropathic pain. However, a pre-emptive effect of adenylate cyclase inhibitor administered before surgery was not observed.     

Perioperative administration of pregabalin for pain after robot-assisted endoscopic thyroidectomy: a randomized clinical trial

Background  

Perioperative administration of pregabalin, which is effective for neuropathic pain, might reduce early postoperative and chronic pain. This randomized, double-blinded, placebo-controlled trial (Clinical Trials.gov ID NCT00905580) was designed to investigate the efficacy and safety of pregabalin for reducing both acute postoperative pain and the development of chronic pain in patients after robot-assisted endoscopic thyroidectomy.     

Different analgesic effects of adenosine between postoperative and neuropathic pain

Background

Adenosine is an endogenous neuromodulator in both the peripheral and central nervous systems. Adenosine inhibits pain signals by hyperpolarizing neuronal membrane.

Methods

To clarify the effects of adenosine on pain signals, we tested intrathecal adenosine injection in two neuropathic pains (spinal cord compression and chronic constriction of sciatic nerve) and postoperative pain (plantar incision).

Results

In all three kinds of pain models, significant shortening of withdrawal latencies to thermal stimulation were detected from 24 h to 1 week after the surgery. Significant improvements of pain sensation were observed in all three models after intrathecal injection of Cl-adenosine 24 h after surgery. At 72 h after surgery, intrathecal Cl-adenosine injection inhibited hyperalgesia in the two neuropathic pain models but not in the postoperative pain model. Adenosine A1R messenger RNA (mRNA) expression significantly decreased in the plantar incision model. Adenosine A1R protein levels also decreased compared with the other two models and normal control.

Conclusions

These results suggest that adenosine effectively inhibits pain signals in neuropathic pain but is less effective in postoperative pain because of the decrease in adenosine A1 receptors.     

Prevalence of neuropathic pain in cases with chronic pain related to spinal disorders

Background

The incidence and characteristics of neuropathic pain associated with spinal disorders have not yet been fully clarified. The purpose of this study was to investigate the prevalence of neuropathic pain and the degree of deterioration of quality of life (QOL) in patients with chronic pain associated with spinal disorders who visited orthopedic outpatient clinics.

Methods

This cross-sectional study was conducted in 1,857 patients recruited from 137 medical institutions nationwide. Participants were men and women aged 20–79 years with a history of spine-related pain for at least 3 months and a visual analog scale (VAS) score of at least 30 in the previous week. Patients were screened using a neuropathic pain screening questionnaire. The degree of QOL deterioration and its correlation with the presence of neuropathic pain were assessed using the Short Form Health Survey with 36 questions (SF-36).

Results

Overall prevalence of neuropathic pain was 53.3 %. It was relatively high in patients with cervical spondylotic myelopathy (77.3 %) and ligament ossification (75.7 %) and relatively low in those with low back pain (29.4 %) and spondylolysis (40.4 %). Only 56.9 % of patients with radiculopathy were diagnosed with neuropathic pain. Logistic regression analysis identified several risk factors, including advanced age, severe pain, disease duration of at least 6 months, and cervical lesions. In QOL assessment, physical functioning, role-physical, role-emotional, and social functioning were severely affected, and this trend was more pronounced in patients who were more likely to have neuropathic pain.

Conclusions

The frequency of neuropathic pain tended to be higher in patients with diseases associated with spinal cord damage and lower in patients with diseases that primarily manifested as somatic pain. A bias toward allodynia symptoms in the screening questionnaire may have resulted in the failure to diagnose neuropathic pain in some patients with radiculopathy. Poor QOL, primarily from the aspect of physical functioning, was demonstrated in patients with neuropathic pain associated with spinal disorders.     

Pain and brachial plexus lesions: evaluation of initial outcomes after reconstructive microsurgery and validation of a new pain severity scale

Background  

Peripheral nerve lesions usually are associated with neuropathic pain. In the present paper, we describe a simple scale to quantify pain after brachial plexus injuries and apply this scale to a series of patients to determine initial outcomes after reconstructive surgery.     

Etanercept attenuates pain-related behavior following compression of the dorsal root ganglion in the rat

Purpose  

TNFα is an inflammatory mediator related to neuropathic pain including sciatica. Much basic research suggests that anti-TNFα therapy may be useful for the treatment of sciatica. The purpose of this study was to clarify the effects of etanercept in a dorsal root ganglion (DRG) compression model.     

Lidocaine treatment during synapse reformation periods permanently inhibits NGF-induced excitation in an identified reconstructed synapse of Lymnaea stagnalis

Purpose  

Nerve growth factor (NGF) has been reported to affect synaptic transmission and cause neuropathic pain. In contrast, lidocaine has been used to reduce neuropathic pain; however, the effect of NGF and lidocaine on spontaneous transmitter release and synapse excitation has not been fully defined. Therefore, the effect of NGF and lidocaine on nerve regeneration, synapse reformation, and subsequent spontaneous transmitter release was investigated. We used Lymnaea stagnalis soma–soma-identified synaptic reconstruction to demonstrate that a transient increase in both frequency and amplitude of spontaneous events of miniature endplate potentials (MEPPs) occurs following NGF treatment and a short burst of action potentials in the presynaptic cell; in addition, the effect of lidocaine on NGF-induced synapse reformation was investigated.     

Nasal inhalation of butorphanol in combination with ketamine quickly elevates the mechanical pain threshold in the model of chronic constriction injury to the sciatic nerve of rat

Background

The aim of the present study is to explore the impact of butorphanol in combination with ketamine via nasal inhalation (NI) on neuropathic pain induced by chronic constriction injury (CCI) to the sciatic nerve in a rat model.

Methods

CCI rats (n = 12) were equally randomized to four groups based on the treatments received as follows: 100 μL of 0.9% normal saline via NI (NS/NI group); 100 μg of butorphanol plus 1 mg of ketamine via NI (B + K/NI group); 100 μg of butorphanol alone via NI (B/NI group); and 100 μg of butorphanol plus 1 mg of ketamine via subcutaneous injection (B + K/SC group). Mechanical pain threshold was measured at 10 min, 30 min, 2 h, 4 h, and 6 h after drug administration.

Results

The mechanical pain threshold in the B + K/NI group was improved significantly 4 h after drug administration as compared with that in the B/NI or B + K/SC group (P < 0.05). The onset and intensity of drug action in the B + K/NI group were better than those of the other two groups, but the duration of drug action was not prolonged.

Conclusions

NI of butorphanol in combination with ketamine quickly elevates the mechanical pain threshold in a rat neuropathic pain model induced by CCI to the sciatic nerve.     

Analgesic Effects of a Single Preoperative Dose of Pregabalin after Laparoscopic Sleeve Gastrectomy

Background  

The treatment of pain in obese patients is always a challenge. These patients have low pain thresholds, and the use of opioids can be especially harmful. Intraoperative nervous fiber section and the high temperatures of electrical scalpels probably contribute to the generation of postoperative neuropathic pain. We hypothesized that an antineuropathic pain drug like pregabalin could be helpful to optimize postoperative analgesia by reducing the requirement for opioids and their associated side effects.     

The effect of multimodal balanced anaesthesia and long term gabapentin on neuropathic pain,nitric oxide and interleukin-1β following breast surgery

ObjectivesTo evaluate the effect of multimodal balanced anaesthesia and gabapentin (6 months) on neuropathic pain qualities, nitric oxide (NO) and interleukin 1-beta (IL-1β).MethodologyThis randomized study was conducted on 50 women scheduled for conservative breast surgery for cancer followed by chemotherapy and/or radiotherapy. Women enrolled into two groups; either to receive balanced general anaesthesia (GA) (control group) or ultrasound guided thoracic paravertebral with GA, multimodal balanced anaesthesia, (intervention group). Nociceptive pain was evaluated for 24 h. Neuropathic pain was evaluated using pain questionnaire 1 month postoperatively and neuropathic pain scale at 1, 3, 6 and 9 months. Gabapentin was prescribed to women reporting neuropathic pain 1 month postoperatively and for 6 months. NO and IL-1β were measured before operation, 1, 3, 6 & 9 months, postoperatively. Their relationship with neuropathic pain was assessed.ResultsNociceptive pain was less in intervention group than control group immediately post operative, 4 h after surgery at rest and 8 h with movement. Neuropathic pain started few days postoperatively, in both groups. Its onset, sites, duration and precipitating factors did not differ between the groups. Sensitive, hot pain and unpleasantness reduced significantly 1 month postoperatively, in intervention group. Two months later, itchy, dull and sharp pain was significantly less in intervention group. At 6 months, most of neuropathic pain items except sharp and deep pain lowered significantly in intervention group. At 9 months, hot and superficial pain was still less in intervention group. NO decreased significantly 1 and 3 months postoperatively, while IL-1β was significantly lower through different times, in intervention group. IL-1β correlated well with neuropathic pain intensity and unpleasantness.ConclusionBreast surgery for cancer was associated with neuropathic pain that continued for 9 months after surgery. Multimodal balanced GA had positive impact on acute nociceptive and neuropathic pain. Gabapentin reduced almost all neuropathic pain qualities.     

An investigation of somatosensory profiles in work related upper limb disorders: a case-control observational study protocol

Background  

Work related upper limb disorders constitute 45% of all occupational diseases and are a significant public health problem. A subgroup, non specific arm pain (NSAP), remains elusive in terms of understanding its pathophysiological mechanisms with its diagnosis based on the absence of specific clinical findings. One commonly proposed theory is that a neural tissue disorder is the primary dysfunction in NSAP and findings from previous studies lend some support to this theory. However, it is not clear if changes identified are simply a consequence of ongoing pain rather than due to specific neural changes. The presence of neuropathic pain has been investigated in several other musculoskeletal conditions but currently, there is no specific diagnostic tool or gold standard which permits an unequivocal diagnosis of neuropathic pain. The purpose of this study is to further describe the somatosensory profiles in patients with NSAP and to compare these profiles to a group of patients with MRI confirmed cervical radiculopathy who have been previously classified as having neuropathic pain.     

Anti-nociceptive effects of caloric restriction on neuropathic pain in rats involves silent information regulator 1

Background

Caloric restriction (CR) increases both average and maximum lifespan, retards physiological signs of ageing, and delays the onset of several diseases and may mediate neuropathic pain. Neuropathic pain seriously affects the quality of life of patients. In this study, we investigated whether CR exerts anti-nociceptive effects on neuropathic pain, and probed its potential mechanisms.

Risk Factors for Peroneal Nerve Injury and Recovery in Knee Dislocation

Background  

Acute knee dislocation is rare but has a high rate of associated neurovascular injuries and potentially limb-threatening complications. These include the substantial morbidity associated with peroneal nerve injury: neuropathic pain, decreased mobility, and considerably reduced function, which not only impairs patient function but complicates treatment.     

Pain mechanisms in chronic pancreatitis: of a master and his fire

Background  

Unraveling the mechanisms of pain in chronic pancreatitis (CP) remains a true challenge. The rapid development of pancreatic surgery in the twentieth century, usage of advanced molecular biological techniques, and emergence of clinician-scientists have enabled the elucidation of several mechanisms that lead to the chronic, complicated neuropathic pain syndrome in CP. However, the proper analysis of pain in CP should include three main arms of mechanisms: “peripheral nociception,” “peripheral/pancreatic neuropathy and neuroplasticity,” and “central neuropathy and neuroplasticity.”     

Effects of Nicotine on Spinal Cord Injury Pain: A Randomized,Double-Blind,Placebo Controlled Crossover Trial

Background:

One factor affecting spinal cord injury (SCI)–related pain may be nicotine. Case reports have described a worsening of neuropathic pain from smoking and relief from abstinence. Neurobiological correlates also implicate the potential effect of nicotine on SCI-related pain.

Method:

The current study employed a randomized, placebo-controlled crossover design to examine the effect of nicotine exposure on subtypes of SCI-related pain among smokers and nonsmokers.

Results:

Whereas nonsmokers with SCI showed a reduction in mixed forms of pain following nicotine exposure, smokers with SCI showed a converse increase in pain with regard to both mixed and neuropathic forms of pain. The exacerbation of pain in chronic nicotine or tobacco users may not only elucidate possible pain mechanisms but may also be of use in smoking cessation counseling among those with SCI.     

Effect of depression and neuropathic pain using questionnaires on quality of life in patients with low back pain; cross-sectional retrospective study

Purpose

The present study investigated the percentage of low back pain (LBP) patients who have depressive symptoms and neuropathic pain and analyzed the effects of these on the quality of life (QOL) in these patients.

Methods

Of the 650 new patients with LBP that visited the hospital between June 2012 and December 2013, 309 patients who completed questionnaires to assess LBP and QOL were included in the study. The questionnaire included demographic items, the self-rated depression scale (SDS)-Zung, the Japanese version of the PainDETECT questionnaire (PDQ-J), numerical pain rating scale (NRS), and QOL assessments. The patients were divided into two groups according to their SDS-Zung scores: a nondepressed group with SDS scores <40 and a depressed group with SDS-Zung scores ≥50.

Results

One hundred twenty-five patients (40.5 %) were classified as nondepressed and 63 (20.4 %) as depressed. The mean PDQ-J score was higher in depressed patients than in nondepressed patients. The frequency of neuropathic pain was greater in depressed patients, with neuropathic pain observed in 17 of the 63 (27 %) depressed LBP patients and 11 of the 125 (9 %) nondepressed LBP patients. The SDS-Zung and PDQ-J scores of LBP patients were correlated significantly (r = 0.261, p < 0.001). Depressed patients had higher pain NRS scores and lower QOL scores compared with nondepressed patients.

Conclusions

Both the depressed patients and those with neuropathic LBP had a higher level of pain, greater pain-related disability, and poorer QOL compared with nondepressed patients. This is the first study to use the SDS-Zung and PDQ-J screening questionnaires to estimate the presence of neuropathic pain associated with depressive symptoms in LBP patients and to evaluate the impact of these on QOL.

     

Low-dose gabapentin as useful adjuvant to opioids for neuropathic cancer pain when combined with low-dose imipramine

Purpose

Painful neuropathic conditions of cancer pain often show little response to nonopioid and opioid analgesics but may be eased by antidepressants and anticonvulsants. Although gabapentin is effective in the treatment of neuropathic pain in patients with cancer, some patients experience intolerable side effects sufficient to warrant discontinuation. The aim of this study was to see whether low-dose gabapentin is effective in treating cancer-related neuropathic pain when combined with low-dose imipramine.

Methods

Fifty-two cancer patients diagnosed as having neuropathic pain were allocated into four groups: G400-I group took gabapentin 200 mg and imipramine 10 mg every 12 h orally; G400 group took gabapentin 200 mg every 12 h orally; G800 group took gabapentin 400 mg every 12 h orally; I group took imipramine 10 mg every 12 h orally.

Results

Low-dose gabapentin–imipramine significantly decreased the total pain score and daily paroxysmal pain episodes. Several patients developed mild adverse symptoms in the four groups, and three patients discontinued treatment due to severe adverse events in the G800 group.

Conclusion

Low-dose gabapentin–antidepressant combination with opioids was effective in managing neuropathic cancer pain without severe adverse effects.