Complex regional pain syndrome (CRPS) presents with pain that is disproportionate to the injury, accompanied by changes in vasodilatation and changes in nutritional or motor function. Despite the lack of evidence for short-term or long-term efficacy, injectable sympathetic blockade has long been used to treat CRPS. however, for many patients with CRPS, the efficacy of sympathetic blockade is short-lived. Surgical or chemical sympathectomy is not universally effective in prolonging analgesia, but produces new pain.
Experiments in animals and humans have shown that post-traumatically injured nerves as well as injured peripheral nerves begin to express adrenergic receptors, and catecholamines cause receptor depolarization to stimulate peripheral nerves and increase pain transmission. These may be the molecular basis for sympathetic maintenance pain.
Botulinum toxin type A (BTA) blocks the release of acetylcholine from cholinergic nerve terminals. This inhibition is long-lasting but not permanent, and it does not cause cytotoxicity or neurological loss. Sympathetic ganglia are cholinergic nerve fibers, and animal studies have shown data that BTA placed in surgically exposed sympathetic nerves produces prolonged sympathetic blockade.
We performed a prospective randomized double-blind study of whether BTA lumbar sympathetic blockade could provide long-term analgesia in patients with sympathetic maintenance pain caused by CRPS in the lower extremities. According to the randomized order, patients received two separate injections of lumbar lumbar sympathetic block: one with 10 ml of 0.5% bupivacaine; and the other with 10 ml of 0.5% bupivacaine + 75 U of BTA. the main observation was the duration of analgesia maintenance.
Patients and methods
All patients met the International Association for the Study of Pain criteria for CRPS type, in addition to:
(1) Spontaneous pain rating greater than 6-10;
(2) Duration of pain for at least 6 months;
(3) Use of at least two non-opioid medications for neuropathic pain (e.g., antitussives, tricyclic antidepressants);
(4) Pain causing functional impairment of the lower extremities;
(5) previous lumbar sympathetic blockade reduces pain by at least 50% and the duration of efficacy is between 5 hours and 2 weeks. Patients were allowed to continue fee taking their current medication but were not allowed to start other new treatments.
Patients were randomized to which injection to receive first, and all participating physicians and patients were unaware of which injection contained BTA, and the date was not blinded until the patient completed the trial.
The lumbar sympathetic block treatment was completed using intermittent fluoroscopy with the tip of a 6-inch 22-gauge puncture needle punctured at the anterolateral border of the second lumbar vertebra.
Patients received a standard LSB injection of 10 mL of 0.5% bupivacaine and a mixed injection of 10 mL of 0.5% bupivacaine + 75 U of BTA. patients did not receive the second medium mixed treatment until 1 month after the pain returned to pre-treatment levels after the first treatment.
VAS scores for pain were performed daily for 7 days prior to injection. Patients continued to record daily VAS until they reported their pain back to starting levels, or for 1 month if less than 1 month, while other adverse events were recorded.
The observed endpoint, the time to return to baseline pain (i.e., “analgesic failure”), was analyzed using Kaplan-Meier analysis.
Results
Nine patients with SMP and CRPS were fully enrolled in this study. The median time to analgesic failure was 71 days (95% confidence interval 12-253 days) in the BTA group and 10 days (95% confidence interval 0-12 days) in the simple group compared with local anesthetic block alone, p < 0.02.
The combination of BTA significantly reduced pain scores compared with local anesthetic block alone, with a mean reduction in VAS of 1.6 points (95% confidence interval 1.2-2.0), p < 0.0001.
This study initially suggests that BTA sympathetic blockade may be a novel and effective treatment for CRPS, and more research is needed to further test the safety and efficacy of this procedure.
Botulinum toxin is an inhibitor of acetylcholine release from cholinergic nerves; this inhibition is long-lasting but not permanent, and it does not lead to cytotoxicity or neurological loss. Cholinergic sympathetic ganglion sympathetic transmission inhibition in the lumbar sympathetic chain may be the mechanism of BTA analgesia.
Studies have reported that lumbar sympathetic radiofrequency and phenol glycerol destruction can be used to treat SMP and CRPS, but have not found a significant advantage over SLB and can produce new pain. In contrast, our study showed that BTA was significantly superior to local anesthetic drug injection alone and there was no nerve remodeling and other complications.
Botulinum toxin was previously used for myofascial pain syndrome and headache. In addition, Argoff predicted that it could be used for neuropathic pain and CRPS, but trials have been lacking. 2008, Ranoux first reported the use of intradermal injection of botulinum toxin for pain caused by peripheral nerve injury and abnormal pain. The results were similar to those reported in the present study, which extends this work and demonstrates its effectiveness for CRPS.
The small number of patients involved in this study, the failure to randomly allow for relevant sequential use of botulinum toxin injections, and the possibility that factors may influence the therapeutic effect of BTA cannot be ruled out. Future studies will also consider assessing a variety of factors such as psychological variables, mood and anxiety affecting pain, and pain baseline.
Conclusion
BTA sympathetic blockade significantly prolongs the duration of analgesia compared to block alone. Further in-depth studies are needed for BTA for the treatment of CRPS.