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

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

BACKGROUNDPain physicians pay close attention to neuropathic pain (NP), since there is currently no ideal treatment. Radial shock wave therapy (RSWT) is a noninvasive treatment to chronic pain of soft tissue disorders. So far, there is no information on the use of RSWT for the treatment of NP. Therefore we observe the effects of RSWT on a NP model induced by chronic constriction injury (CCI) in rats.

METHODSFour different energy densities (1.0, 1.5, 2.0 and 2.5 bar) RSWT administered as a single session or repeated sessions in rats with NP induced by CCI of the sciatic nerve. The analgesic effect was assessed by measuring mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). The safety was assessed through calculating sciatic functional index (SFI).

RESULTSMWT and TWL increased after a single session of RSWT from day 1 to day 5 but returned to baseline levels by day 10. Following repeated sessions of RSWT, both the MWT and TWL were significantly higher than NP group (P < 0.01) for at least 4 weeks. In addition, no significant changes of SFI were observed in any groups after repeated sessions of RSWT and no increased pain or other side effects in any animals.

CONCLUSIONSA single session of RSWT is rapidly effective in the treatment of CCI, but the efficacy maintained in a short period. However, repeated sessions of RSWT have prolonged efficacy.

Animals ; Chronic Pain ; therapy ; High-Energy Shock Waves ; Male ; Neuralgia ; therapy ; Rats, Sprague-Dawley ; Sciatic Nerve ; physiopathology

Activation of microglia plays a vital role in the initiation and maintenance of specific neuropathic pain states. By activating microglia in central nervous system, Toll-like receptor 4 (TLR4) can promote the release of proinflammatory cytokines and neuroactive compounds, participate in the initiation and maintenance of neuropathic pain, and trigger the opiate side effects. Therefore, TLR4 may be a potential therapeutic target for neuropathic pain. Inhibition of TLR4 has shown some biological effects in neuropathic pain models and ibudilast (the TLR4 pathway-inhibiting agent) has been approved for for phase 2 clinical trials. This article briefly reviews the structure, function, and mechanism of TLR4 as well as the development of TLR4-targeted drugs.
Humans ; Neuralgia ; drug therapy ; physiopathology ; Toll-Like Receptor 4 ; antagonists & inhibitors ; physiology

OBJECTIVETo observe the differences of therapeutic effect in primary trigeminal neuralgia (PTN) of hyperactive of liver yang type treated by deep and shallow puncturing at Xiaguan (ST 7).

METHODSSixty-three cases of PTN of hyperactive of liver yang type were randomly divided into a deep puncturing group (32 cases) and a shallow puncturing group (31 cases). Xiaguan (ST 7) of affected region, Hegu (LI 4) and Taichong (LV 3) of bilateral sides, Cuanzhu (BL 2), Sibai (ST 2) and Jiachengjiang (Extra) relevant to the affected branch of nerve stem were selected in both groups. In deep puncturing group, Xiaguan (ST 7) was punctured to the depth of spheno-palatine ganglion (SPG); Cuanzhu (BL 2), Sibai (ST 2) and Jiachengjiang (Extra) were respectively punctured to the depth of supraorbital foramen, infraorbital foramen and mental foramen. In shallow group, routine puncturing was applied; the needles were connected with G6805 electric acupuncture apparatus, and switched on for 30 min every time; the treatment was applied every other day. Pain index, traditional Chinese medicine symptoms index and clinical therapeutic effect were observed after 2 courses of treatment.

RESULTSIn deep puncturing group, the VAS scores and the traditional Chinese medicine symptoms scores (pain degree, pain frequency, upsetting, conjunctival congestion, bitter mouth and hypochondriac pain) after treatment were much more lower than those before treatment (all P < 0.01); in shallow puncturing group, except hypochondriac pain (P > 0.05), other indices above after treatment were obviously lower than those before treatment (P < 0.01, P < 0.05). Compared with the indices in both groups after treatment, the VAS scores, the pain degree, conjunctival congestion and total scores of traditional Chinese medicine symptoms in deep puncturing group were more significant (all P < 0.05). The total effective rate was 93.8% (30/32) in deep puncturing group, superior to that of 87.1% (27/31) in shallow puncturing group (P < 0.05). No any adverse reaction was observed in both groups.

CONCLUSIONThe therapeutic effect of trigeminal neuralgia of hyperactive of liver yang type treated with electroacupuncture is remarkable, and deep puncturing at Xiaguan(ST 7) to SPG is more effective than routine puncturing.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Diagnosis, Differential ; Female ; Humans ; Liver ; physiopathology ; Male ; Middle Aged ; Trigeminal Neuralgia ; diagnosis ; physiopathology ; therapy

OBJECTIVETo provide a set of the self-help and mutual-aid treatment with moxibustion to deal with myofasicial pain syndrome (MPS) of the back for the military soldiers.

METHODSFifty-eight cases were randomly devided into a moxibustion group (30 cases) and a plaster application group (28 cases). In the moxibustion group, the suspended moxibustion was applied to Yanglingquan (GB 34) for 15 min. The moxibustion massage device was used to massage the pain area. Under the physician's guides, the self-help or mutual-aid treatment was adopted. In the plaster application group, Goupi Gao (a black plaster used in TCM) was used on the local pain area. The treatment was given once every day in either group, lasting for 5 days. The clinical symptom scale, clinical physical sign scale, functional disturbance scale, functional disturbance index, comprehensive economic benefit and the others were adopted to analyze and compare the clinical efficacies between the two groups.

RESULTSBoth moxibustion and the plaster application achieved a certain efficacy on MPS of the back in the soldiers and either of them received the obvious improvements in the clinical symptoms, physical signs and functional disturbance (P < 0.01, P < 0.05). The results in the moxibustion group were superior to those in the plaster application group (P < 0.01, P < 0.05). In terms of the comprehensive economic benefit index, the result in the moxibustion group was better than that in the plaster application group. The total effective rate was 96.7% (29/30) in the moxibustion group and was 35.7% (10/28) in the plaster application group. The efficacy in the moxibustion group was superior to that in the plaster application group (P < 0.01).

CONCLUSIONThe self-help or mutual-aid treatment with moxibustion achieves the satisfactory clinical efficacy on MPS of the back in the military soldiers. It reduces the conventional medical cost and the military medical expenditure. This therapeutic approach is suitable to be promoted in the military.

Adult ; Facial Neuralgia ; physiopathology ; therapy ; Humans ; Military Personnel ; Moxibustion ; methods ; Young Adult

OBJECTIVETo observe the clinical efficacy on primary trigeminal neuralgia treated with joint needling method at the trigger point.

METHODSOne hundred and three cases of primary trigeminal neuralgia were divided into a joint needling group (53 cases) and a conventional needling group (50 cases) according to the visit sequence. In the joint needling group, the joint needling method was used at the trigger point in the mandibular joint [the positive point near to Xiaguan (ST 7)]; the conventional needling was used at Hegu (LI 4), Waiguan (TE 5), Taichong (LR 3) and Neiting (ST 44). In the conventional needling group, Xiaguan (ST 7) and Fengchi (GB 20) were used and the supplementary acupoints were selected according to the involved branches of trigeminal nerve. The conventional needling method was used. The Visual Analogue Scale (VAS) and the score of trigeminal neuralgia were adopted to assess the pain severity and the comprehensive symptoms before treatment and after the 1st and 2nd sessions of treatment separately. The efficacy was assessed.

RESULTSAfter the 1st and 2nd sessions of treatment, VAS score and the comprehensive symptom score were reduced obviously as compared with those before treatment in either group (P < 0.05, P < 0.01). The score reducing in the joint needling group was much superior to that in the conventional needling group (both P < 0.05). The total effective rate was 90.6% (48/53) and 72. 0% (36/50) in the joint needling group and the conventional needling group respectively. The effect in the joint needling group was better than that in the conventional needling group (P < 0.05).

CONCLUSIONThe joint needling method at the trigger point achieves the significant efficacy on primary trigeminal neuralgia, which is superior to that with the conventional needling method.

Acupuncture Points ; Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neuralgia ; physiopathology ; therapy ; Trigeminal Nerve ; physiopathology ; Trigeminal Neuralgia ; physiopathology ; therapy ; Trigger Points ; physiopathology ; Young Adult

OBJECTIVE: To investigate the effect of intrathecal sufentanil and protein kinase C inhibitor on pain threshold and the expression of N-methyl-D-aspartate receaptors (NMDAR)/calcitonin generelated peptide (CGRP) in spinal dorsal horn in rats with neuropathic pain. METHODS: Fifty-four healthy male Sprague-Dawley rats were randomly divided into 6 groups (9 in each group). The rats in the sham group(Group S) + spared nerve injury (SNI), SP+SNI, and P+SNI were intrathecally injected sufentanil (1 μg), sufentanil (1 μg) and chelerythrine chloride (11 μg), chelerythrine chloride (11 μg) followed by 10 μL normal saline once every day for 14 days postoperatively, respectively. Similarly, rats in the control group (Group C), the sham group (Group S), and SNI model group (Group SNI) were intrathecally injected 20 μL normal saline in the uniform interval. Pain behaviours were measured on Day 1 pre-surgery and on Day 1, 2, 7, and 14 after the intrathecal injection. The expressions of NMDAR and CGRP in the spinal dorsal horn of L5 segment were determined by immunohistochemistry on Day 2, 7, and 14 after the intrathecal injection. RESULTS: Compared with Group C and Group S, mechanical allodynia threshold in group SNI was decreased after the surgery (P<0.01), and expressions of NMDAR and CGRP immunoreactive soma in the spinal dorsal horn was significantly increased (P<0.01). Mechanical stimulation pain threshold was elevated in Group S+SNI, Group P+SNI, and Group SP+SNI compared with Group SNI (P<0.01), while expressions of NMDAR and CGRP immunoreactive soma in Group S+SNI, Group P +SNI, and Group SP+SNI were significantly decreased (P<0.05 or 0.01). CONCLUSION Intrathecal administration of sulfentanil and protein kinase C inhibitor can provide significant antinociception in rats with neuropathic pain and obviously inhibit the upregulation of NMDAR and CGRP expressions in the spinal dorsal horn of SNI rat models.
Animals ; Benzophenanthridines ; administration & dosage ; Calcitonin Gene-Related Peptide ; metabolism ; Injections, Spinal ; Male ; Neuralgia ; drug therapy ; metabolism ; physiopathology ; Pain Measurement ; Posterior Horn Cells ; metabolism ; Protein Kinase C ; antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; metabolism ; Sufentanil ; administration & dosage