RESUMO
Objective:To investigate the mechanism of Three Handing-Three Points on pain function in sciatic nerve injury rats by observing the changes of chemokine (C-X3-C motif) ligand 1, CX3CL1)/chemokine (C-X3-C motif) receptor 1 (CX3CR1) protein and mRNA expression in spinal dorsal horn. Methods:A total of 74 male Sprague-Dawley rats were randomly divided into normal group (n= 12), sham group (n = 24), model group (n = 25), and Three Handing-Three Points group (Tuina group,n = 13). The model group and Tuina group prepared the sciatic nerve injury model. The sham group exposed sciatic nerve only. Tuina group received Tuina on Yinmen (BL37), Chengshan (BL57) and Yanglingquan (GB34) with Tuina manipulation emulator. The photothermal pain threshold was measured seven days after modeling and after 20 days of intervention; cumulative pain score was measured seven days after modeling, and after ten days and 20 days of intervention. The spinal dorsal horn tissues were extracted to detect the protein and mRNA expression of CX3CL1/CX3CR1 with Western blotting and RT-PCR seven days after modeling and after 20 days of intervention. The microglia morphology in spinal dorsal horn was observed with immunofluorescence after 20 days of intervention. Results:Seven days after modeling, compared with the normal group, the photothermal pain tolerance threshold increased in the model group and the sham group (P < 0.05); compared with the sham group, the cumulative pain score increased in the model group and Tuina group (P < 0.05). After ten days of intervention, the cumulative pain score was lower in Tuina group than in the model group (P < 0.05). After 20 days of intervention, both the photothermal pain tolerance threshold and cumulative pain score were lower in Tuina group than in the model group (P < 0.05). There was no significant difference in the expression of CX3CL1/CX3CR1 protein and mRNA on the seven days after modeling and after 20 days of intervention (P > 0.05). The microglia in the model group were partially activated or completely activated, while those in Tuina group were unactivated or partially activated after 20 days of intervention. Conclusion:Three Handing-Three Points can improve the pain function of sciatic nerve injured rats, which may associate with regulating microglia through the pathway other than CX3CL1/CX3CR1.
RESUMO
Objective: Based on recent success of intra-articular (IA) Botulinum neurotoxin type A (BoNT/A; OnabotulinumtoxinA) in patients with osteoarthritis, we examined if repeat IABoNT/ A is an effective antinociceptive in patients with refractory arthroplasty pain. Methods: 11 patients with refractory chronic arthroplasty joint pain without any evidence of infection or prosthesis loosening were referred by orthopedic surgeons. After discussion of off-label use, each patient underwent IA injection of BoNT/A, repeated based on return of pain on numeric rating scale (NRS) and functional limitation on composite validated scales, Western Ontario McMaster Osteoarthritis index (WOMAC) or Shoulder Pain and Disability (SPADI). Results: 11 patients (10 men, 1 woman) with 14 painful arthroplasty joints (3 bilateral; 12 knee and 2 shoulder) underwent ≥1 IA-BoNT/A injections (8 joints injected once, one joint injected twice only, five joints injected thrice) with doses ranging 100-300 units. Mean age was 68 years (standard deviation, 12) and follow-up ranged 1-28 months. Clinically meaningful reduction of 2-units in pain severity and really meaningful reduction in pain severity (50% reduction) were reported by 6/11 patients (6/13 joints) and 3/11 patients (3/13 joints), respectively, 1 month after the first IA-BoNT/A (100-units each). Significant improvements were noted in composite functional scales (WOMAC/SPADI). Pain relief was sustained at 3-4 month follow-up and was reproducible in those who received repeat injections. No significant adverse events were seen in any patients. Conclusions: A single intra-articular injection of BoNT/A improved pain and function in patients with chronic, refractory painful knee or shoulder arthroplasty, which sustained with repeat injections. Patients, who were refractory to the first injection, did not respond to subsequent injections of higher dose of IA-BoNT/A.