Investigation of pain requires measurements of nociceptive sensitivity and other pain-related behaviors. Recent studies have indicated the superiority of gait analysis over traditional evaluations (e.g., skin sensitivity and sciatic function index [SFI]) in detecting subtle improvements and deteriorations in animal models. Here, pain-related gait parameters, whose criteria include (1) alteration in pain models, (2) correlation with nociceptive threshold, and (3) normalization by analgesics, were identified in representative models of neuropathic pain (spared nerve injury: coordination data) and inflammatory pain (intraplantar complete Freund's adjuvant: both coordination and intensity data) in the DigiGait™ and CatWalk™ systems. DigiGait™ had advantages in fixed speed (controlled by treadmill) and dynamic SFI, while CatWalk™ excelled in intrinsic velocity, intensity data, and high-quality 3D images. Insights into the applicability of each system may provide guidance for selecting the appropriate gait imaging system for different animal models and optimization for future pain research.
Analgesics ; administration & dosage ; Animals ; Freund's Adjuvant ; administration & dosage ; Gait ; drug effects ; Gait Analysis ; methods ; Image Processing, Computer-Assisted ; Inflammation ; chemically induced ; Male ; Neuralgia ; physiopathology ; prevention & control ; Pain ; etiology ; physiopathology ; prevention & control ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the abnormalities in regional homogeneity of brain activity in patients with diabetic peripheral neuropathy (DPN) using resting-state functional magnetic resonance imaging (rs-fMRI) and explore the association between brain activity changes and DPN. METHODS: A regional homogeneity (ReHo) approach was used to compare the local synchronization of rs-fMRI signals among 20 patients with painful DPN, 16 patients with painless DPN, and 16 type 2 diabetic patients without DPN (non-DPN group). RESULTS: Compared with the those without DPN, the patients with painful DPN showed high ReHo in the left inferior temporal gyrus and the right central posterior gyrus, and low ReHo in the posterior cingulate gyrus, right inferior parietal gyrus, and the left superior parietal gyrus ( < 0.05);the patients with painless DPN group showed high ReHo in the left inferior temporal gyrus, the right middle temporal gyrus, and the right superior frontal gyrus, and low ReHo in the left thalamus ( < 0.05).No significant differences in ReHo were found between the patients with painful DPN and painless DPN (>0.05). CONCLUSIONS The patients with DPN have altered ReHo in multiple brain regions and impairment of a default mode network, for which the left temporal gyrus may serve as a functional compensatory brain area. ReHo disturbance in the central right posterior gyrus may play a central role in the pain symptoms associated with painful DPN.
Brain ; diagnostic imaging ; physiopathology ; Brain Mapping ; methods ; Diabetic Neuropathies ; physiopathology ; Gyrus Cinguli ; diagnostic imaging ; physiopathology ; Humans ; Magnetic Resonance Imaging ; methods ; Neuralgia ; physiopathology ; Temporal Lobe ; diagnostic imaging ; physiopathology

Trigeminal neuralgia (TN) is a kind of recurrent transient and severe pain that is limited to the trigeminal nerve in one or more branches. The clinical incidence of TN is high, which seriously affects the quality of life of the patients and is difficult to cure. The present study investigated the effects of tetramethylpyrazine (TMP) on TN induced by chronic constriction injury of the infraorbital nerve (ION-CCI) in rats. Adult male Sprague-Dawley rats were randomly assigned to four groups: sham, sham treated with TMP (Sham+TMP), TN model (TN), and TN treated with TMP (TN+TMP). The rat TN model was established by ION-CCI and TMP (50 mg/kg) was injected intraperitoneally once a day for 2 weeks after operation. The mechanical response threshold was tested by the electronic von Frey filaments. The expression of CGRP in the trigeminal ganglia (TGs) of rats on the operative side was detected by RT-PCR, immunohistochemical staining and Western blot. In 15 days after operation, TN group showed a robust decrease in mechanical response threshold as compared with sham group. From day 9 to day 15 after operation, TMP treatment significantly suppressed the TN-induced mechanical hyperalgesia (P < 0.05). On day 15 after operation, RT-PCR, immunohistochemical staining and Western blot analysis showed an obvious increase in expression level of CGRP in TGs of TN group compared with sham group, which was downregulated by TMP treatment (P < 0.05). These results suggested that TMP might have a therapeutic potential for the treatment of TN through regulating CGRP expression in the TGs.
Animals ; Constriction ; Hyperalgesia ; drug therapy ; Male ; Pyrazines ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Trigeminal Ganglion ; physiopathology ; Trigeminal Neuralgia ; drug therapy

Occipital neuralgia is defined by the International Headache Society as paroxysmal shooting or stabbing pain in the dermatomes of the greater or lesser occipital nerve. Various treatment methods exist, from medical treatment to open surgical procedures. Local injection with corticosteroid can improve symptoms, though generally only temporarily. More invasive procedures can be considered for cases that do not respond adequately to medical therapies or repeated injections. Radiofrequency lesioning of the greater occipital nerve can relieve symptoms, but there is a tendency for the pain to recur during follow-up. There also remains a substantial group of intractable patients that do not benefit from local injections and conventional procedures. Moreover, treatment of occipital neuralgia is sometimes challenging. More invasive procedures, such as C2 gangliotomy, C2 ganglionectomy, C2 to C3 rhizotomy, C2 to C3 root decompression, neurectomy, and neurolysis with or without sectioning of the inferior oblique muscle, are now rarely performed for medically refractory patients. Recently, a few reports have described positive results following peripheral nerve stimulation of the greater or lesser occipital nerve. Although this procedure is less invasive, the significance of the results is hampered by the small sample size and the lack of long-term data. Clinicians should always remember that destructive procedures carry grave risks: once an anatomic structure is destroyed, it cannot be easily recovered, if at all, and with any destructive procedure there is always the risk of the development of painful neuroma or causalgia, conditions that may be even harder to control than the original complaint.
Anesthetics/therapeutic use ; Botulinum Toxins/therapeutic use ; Electric Stimulation ; Humans ; Magnetic Resonance Imaging ; Nerve Block ; Neuralgia/*diagnosis/surgery/therapy ; Spinal Nerves/anatomy & histology/*physiopathology ; Steroids/pharmacology

OBJECTIVETo investigate the clinical outcomes of semicircular decompression in treating old thoracolumbar fractures and intractable neuropathic pain.

METHODSFrom September 2009 to September 2013, 21 patients with old thoracolumbar fracture and intractable neuropathic pain were treated with semicircular decompression. Among initial surgery, posterior pedicle screw fixation was used in these patients, with or without laminectomy. All patients were male, range in age from 20 to 28 years old with an average of (25.00±2.38) years. Vertebral body residual bone block resulted in intra-spinal placeholder more than 50%. All patients were complete spinal cord injury (ASIA grade) or cauda equina injury. VAS scores was from 6 to 10 points with the mean of 7.14±0.91. In these patients, MRI, CT, X-rays were performed; denomination and dosage of analgesics were recorded; nerve function and pain status were respectively evaluated by ASIA grade and VAS score before and after operation.

RESULTSAll patients were followed up from 8 to 32 months with an average of (17.29±6.02) months. All bone fragments of spinal canal were removed and spinal cord decompressions were achieved. At final follow-up, VAS scores were from 0 to 8 points with an average of (2.43±2.46) points, and were obviously reduced than peroperative data (P<0.05). Eleven cases of them stopped analgesic intake and 7 cases reduced using. Three patients' symptoms and VAS scores were not improved.

CONCLUSIONOld thoracolumbar fractures and intractable neuropathic pain need receive imaging examination as soon as possible and consider semicircular decompression therapy if bone fragments were in vertebral canal and spinal canal stenosis existed. This therapy can effectively relieve pain and profit nerve functional recovery.

Adult ; Decompression, Surgical ; methods ; Humans ; Lumbar Vertebrae ; injuries ; surgery ; Male ; Neuralgia ; etiology ; surgery ; Pain, Intractable ; etiology ; surgery ; Spinal Fractures ; physiopathology ; surgery ; Thoracic Vertebrae ; injuries ; surgery ; Visual Analog Scale ; Young Adult

Nefopam has a pharmacologic profile distinct from that of opioids or other anti-inflammatory drugs. Several recent studies demonstrate that nefopam has a mechanism of action similar to those of anti-depressants and anticonvulsants for treating neuropathic pain. The present study investigates the mechanical antiallodynic effect of nefopam using immunohistochemical study and western blot analysis in a rat neuropathic pain model. Twenty-eight male Sprague-Dawley rats were subjected to left fifth lumbar (L5) spinal nerve ligation and intrathecal catheter implantation, procedures which were not performed on the 7 male Sprague-Dawley rats in the sham surgery group (group S). Nefopam, either 10 or 100 microg/kg (group N10 or N100, respectively), and normal saline (group C) were intrathecally administered into the catheter every day for 14 days. The mechanical allodynic threshold of intrathecal nefopam was measured using a dynamic plantar aesthesiometer. Immunohistochemistry targeting cluster of differentiation molecule 11b (CD11b) and glial fibrillary acidic protein (GFAP) was performed on the harvested spinal cord at the level of L5. Extracellular signal-regulated kinase 1/2 (ERK 1/2) and cyclic adenosine monophosphate response element binding protein (CREB) were measured using western blot analysis. The N10 and N100 groups showed improved mechanical allodynic threshold, reduced CD11b and GFAP expression, and attenuated ERK 1/2 and CREB in the affected L5 spinal cord. In conclusion, intrathecal nefopam reduced mechanical allodynia in a rat neuropathic pain model. Its mechanical antiallodynic effect is associated with inhibition of glial activation and suppression of the transcription factors' mitogen-activated protein kinases in the spinal cord.
Analgesics, Non-Narcotic/administration & dosage ; Animals ; Dose-Response Relationship, Drug ; Hyperalgesia/*drug therapy/etiology/*physiopathology ; Injections, Spinal ; Male ; Nefopam/*administration & dosage ; Neuralgia/complications/*drug therapy/*physiopathology ; Pain Measurement/drug effects ; Pain Perception/*drug effects ; Rats ; Rats, Sprague-Dawley ; Treatment Outcome

PURPOSE: Osteoarthritic (OA) pain is largely considered to be inflammatory pain. However, during the last stage of knee OA, sensory nerve fibers in the knee are shown to be significantly damaged when the subchondral bone junction is destroyed, and this can induce neuropathic pain. Several authors have reported that tumor necrosis factor-alpha (TNFalpha) in a knee joint plays a crucial role in pain modulation. The purpose of the current study was to evaluate the efficacy of etanercept, a TNFalpha inhibitor, for pain in knee OA. MATERIALS AND METHODS: Thirty-nine patients with knee OA and a 2-4 Kellgren-Lawrence grading were evaluated in this prospective study. Patients were divided into two groups; hyaluronic acid (HA) and etanercept injection. All patients received a single injection into the knee. Pain scores were evaluated before and 4 weeks after injection using a visual analogue scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and they were compared between the groups. RESULTS: Before injection, VAS and WOMAC scores were not significantly different between the groups (p>0.05). Significant pain relief was found in the etanercept group at 1 and 2 weeks by VAS, and at 4 weeks by WOMAC score, compared with the HA group (p<0.05). No adverse events were observed in either group. CONCLUSION: Direct injection of etanercept into OA knee joints was an effective treatment for pain in moderate and severe OA patients. Furthermore, this finding suggests that TNFalpha is one factor that induces OA pain.
Aged ; Etanercept/*administration & dosage/therapeutic use ; Female ; Humans ; Hyaluronic Acid/administration & dosage/*therapeutic use ; Injections, Intra-Articular ; Knee Joint/physiopathology ; Male ; Middle Aged ; Neuralgia/drug therapy ; Osteoarthritis, Knee/*drug therapy ; Pain Measurement ; Prospective Studies ; Severity of Illness Index ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; Viscosupplements/administration & dosage/*therapeutic use ; Visual Analog Scale

PURPOSE: The TWIK-related spinal cord K+ channel (TRESK) has recently been discovered and plays an important role in nociceptor excitability in the pain pathway. Because there have been no reports on the TRESK expression or its function in the dorsal horn of the spinal cord in neuropathic pain, we analyzed TRESK expression in the spinal dorsal horn in a spinal nerve ligation (SNL) model. MATERIALS AND METHODS: We established a SNL mouse model by using the L5-6 spinal nerves ligation. We used real-time polymerase chain reaction and immunohistochemistry to investigate TRESK expression in the dorsal horn and L5 dorsal rot ganglion (DRG). RESULTS: The SNL group showed significantly higher expression of TRESK in the ipsilateral dorsal horn under pain, but low expression in L5 DRG. Double immunofluorescence staining revealed that immunoreactivity of TRESK was mostly restricted in neuronal cells, and that synapse markers GAD67 and VGlut2 appeared to be associated with TRESK expression. We were unable to find a significant association between TRESK and calcineurin by double immunofluorescence. CONCLUSION: TRESK in spinal cord neurons may contribute to the development of neuropathic pain following injury.
Animals ; Disease Models, Animal ; Hyperalgesia ; Ligation ; Male ; Neuralgia/*metabolism/physiopathology ; Neurons/metabolism ; Nociceptors ; Pain/metabolism/*physiopathology ; Potassium Channels/*metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Spinal Cord Dorsal Horn/*metabolism ; Spinal Nerves/*injuries

OBJECTIVETo study the possible mechanisms of chronic nonbacterial prostatitis (CNP) pain.

METHODSCNP models were established in male Wistar rats by the autoimmune method. Then the paw withdrawal threshold (PWT) was detected using the Von Frey filament, prostate pathological examination was conducted, the expressions of substance P (SP) and transient receptor potential vanilloid 1 (TRPV1) in the prostate tissue and L5-S2 spinal segments were determined by immunohistochemistry and their correlations were analyzed.

RESULTSCompared with the control group, the CNP model rats showed markedly decreased PWT (P < 0.05) and obvious inflammation in the prostate tissue, with significant differences in the scope of lesion and interstitial lymphocyte infiltration (P < 0.05). The expressions of SP and TRPV1 in the prostate and spinal cord dorsal horn L5-S2 were remarkably upregulated in the models as compared with the control rats (P < 0.05). However, the expression of SP in the prostate was not correlated with that in the spinal cord (r = 0.099, P = 0.338), nor was that of TRPV1 (r = 0.000, P = 0.5).

CONCLUSIONSP and TRPV1 were involved in the formation and persistence of pain in CNP rats through their upregulated expressions in the L5-S2 spinal segments.

Animals ; Lumbosacral Region ; Male ; Neuralgia ; metabolism ; physiopathology ; Pain ; metabolism ; physiopathology ; Prostate ; metabolism ; Prostatitis ; metabolism ; physiopathology ; Rats ; Rats, Wistar ; Spinal Cord ; metabolism ; Substance P ; metabolism ; TRPV Cation Channels ; metabolism

Adult ; Aged ; Cauda Equina ; pathology ; physiopathology ; Female ; Humans ; Hypesthesia ; pathology ; Male ; Middle Aged ; Neuralgia ; pathology ; physiopathology ; Spinal Cord Injuries ; pathology ; physiopathology