Direct Inhibition of Microglia Activation by Pretreatment With Botulinum Neurotoxin A for the Prevention of Neuropathic Pain

Peripheral injection of botulinum neurotoxin A (BoNT/A) has been demonstrated to have a long-term analgesic effect in treating neuropathic pain. Around peripheral nerves, BoNT/A is taken up by primary afferent neurons and inhibits neuropeptide release. Moreover, BoNT/A could also be retrogradely transported to the spinal cord. Recent studies have suggested that BoNT/A could attenuates neuropathic pain by inhibiting the activation of spinal glial cells. However, it remains unclear whether BoNT/A directly interacts with these glial cells or via their interaction with neurons. Our aim here is to determine the direct effect of BoNT/A on primary microglia and astrocytes. We show that BoNT/A pretreatment significantly inhibits lipopolysaccharide (LPS) -induced activation and pro-inflammatory cytokine release in primary microglia (1 U/mL BoNT/A in medium), while it has no effect on the activation of astrocytes (2 U/mL BoNT/A in medium). Moreover, a single intrathecal pre-administration of a low dose of BoNT/A (1 U/kg) significantly prohibited the partial sciatic nerve ligation (PSNL)- induced upregulation of pro-inflammatory cytokines in both the spinal cord dorsal horn and dorsal root ganglions (DRGs), which in turn prevented the PSNL-induced mechanical allodynia and thermal hyperalgesia. In conclusion, our results indicate that BoNT/A pretreatment prevents PSNL-induced neuropathic pain by direct inhibition of spinal microglia activation.

Effects of ultrasound-assisted botulinum neurotoxin-A injection in patients with bruxism and masseter hypertrophy

Objectives: This study aims to explore effects of ultrasound-assisted injection of the botulinum neurotoxin-A (BoNT-A) on muscle thickness (MT) in patients with masseter hypertrophy. Patients and methods: Between December 2018 and December 2019, a total of 20 patients (3 males, 17 females; mean age: 28±6.9 years; range, 18 to 42 years) with bruxism who underwent BoNT-A injections were reviewed retrospectively. The patients were treated using individualized injection dosages and sites. Assessment methods included length between the tragus and the angle of the mouth, maximal bite force, and MT of the masseter muscle. Follow-up data were collected from the hospital electronic database. Results: There were 26 masseter muscles with masseter hypertrophy in 20 patients. There was a significant difference in ultrasonographic measurements of the relaxed and contracted masseter muscles between the baseline and two weeks, one month and three months after the treatment (p<0.05). In the ultrasonographic measurement of the relaxed masseter muscle, post-treatment third month values significantly differed from the second week values. The differences in the measurement of the line between the tragus and the angle of the mouth between the baseline and two weeks, one month and three months after the treatment were statistically significant (p<0.05). In the maximal bite force measurements, no significant difference was observed between the baseline and post-intervention measurements (p>0.05). Conclusion: The MT decreases after a single dose of BoNT-A injection in patients with masseter muscle hypertrophy and ultrasonography is a convenient imaging modality for BoNT-A injection to the masseter.

Intratracheal inoculation of AHc vaccine induces protection against aerosolized botulinum neurotoxin A challenge in mice

Botulinum neurotoxin (BoNT), produced by Clostridium botulinum, is generally known to be the most poisonous of all biological toxins. In this study, we evaluate the protection conferred by intratracheal (i.t.) inoculation immunization with recombinant Hc subunit (AHc) vaccines against aerosolized BoNT/A intoxication. Three AHc vaccine formulations, i.e., conventional liquid, dry powder produced by spray freeze drying, and AHc dry powder reconstituted in water are prepared, and mice are immunized via i.t. inoculation or subcutaneous (s.c.) injection. Compared with s.c.-AHc-immunized mice, i.t.-AHc-immunized mice exhibit a slightly stronger protection against a challenge with 30,000× LD50 aerosolized BoNT/A. Of note, only i.t.-AHc induces a significantly higher level of toxin-neutralizing mucosal secretory IgA (SIgA) production in the bronchoalveolar lavage of mice. In conclusion, our study demonstrates that the immune protection conferred by the three formulations of AHc is comparable, while i.t. immunization of AHc is superior to s.c. immunization against aerosolized BoNT/A intoxication.

Mechanism and Priority of Botulinum Neurotoxin A versus Sacral Neuromodulation for Refractory Overactive Bladder: A Review

<b><i>Background:</i></b> The treatment of common overactive bladder (OAB) has reached a consensus, but there is not a clear answer to the treatment of refractory OAB (ROAB). ROAB is defined as nonresponsive to treatment with behavioural and oral therapies. The disease can influence the physical and mental health of patients, cause poor quality of life, and create an urgent socio-economic burden. With the advancement of medical treatment, the treatment of OAB has improved significantly in the last 2 decades, especially ROAB, by the usage of botulinum neurotoxin A (BoNT-A) and sacral neuromodulation (SNM). Many studies have demonstrated their effectiveness and safety. However, which therapy is the optimal method remains unclear for patients with ROAB, and the exact mechanism involved in the procedures is still unknown. <b><i>Summary:</i></b> This review is to clarify the mechanisms, advantages, and disadvantages of SNM and BoNT-A in treatment of ROAB, and determine whether there is an order effect of SNM and BoNT-A in managing ROAB. <b><i>Key Messages:</i></b> BoNT-A and SNM mainly act on the peripheral nervous system and central nervous system, respectively. But BoNT-A and SNM may partly act on the central and peripheral nervous systems, separately. SNM may be a better choice than BoNT-A in the long time. At the same time, BoNT-A and SNM can treat the ROAB as the first and next steps, and the sequence of both would not affect the effectiveness of each other.