Table 1.
Summary of studies on BoNT effects on pain-related receptors.
| Receptor type | Model (in vivo, in vitro) | Human/Animal/Cells | BoNT type injection site/Dose | Result | Reference |
|---|---|---|---|---|---|
| TRPV1 | In vivo | Rat | BoNT/A/Subcutaneously into ophthalmic division of trigeminal ganglion/0.25, 0.5, and 5 ng/kg | Cleavage of SNAP-25, reduction of TRPV1 levels and transmission to cell membrane of trigeminal ganglion neurons | 66 |
| TRPV1 | In vivo | Rat/Spinal ventral root transection model | BoNT/A/Subcutaneously/10 and 20 unit/kg | Reduction of TRPV1 expression in DRG neurons | 67 |
| TRPV1 and TRPA1 | In vivo | Rat | BoNT/A/extracranial injection/outside the calvaria/5 unit | Inhibition of synaptic vesicles attaching comprising TRPA1 and TRPV1 channels into the cell surface | 68 |
| TRPV1 | In vitro | Mouse/Embryonic DRG neurons | BoNT/A/1 nM | Colocalization of TRPV1 with SNAP-25 and BoNT/A in cell membrane | 69 |
| TRPV1 | In vivo | Rat/Adjuvant-arthritis pain model | BoNT/A/Intra-articulary/1, 3 and10 unit | Cleavage of SNAP-25, reduction of TRPV1 expression in DRG neurons | 70 |
| TRPV4 and TRPM3 | In vivo | Rat/ION-CCI model | BoNT/A/Subcutaneously/3 and10 unit | Reduction of TRPV1 expression in the trigeminal spinal subnucleus caudalis | 71 |
| Sodium | In vitro | Rat/Hippocampus and DRG cells | BoNT/A/10 p.m. | Inhibition of membrane Na+-channel activity | 72 |
| Sodium (NaV1.7) | In vivo | Rat/Trigeminal neuropathic pain | BoNT/A/Subcutaneously/10 and 20 unit/kg | Inhibition of Nav1.7 overexpression | 73 |
| Calcium (CaV3.2) | In vivo | Rat/SCI model | BoNT/A/Intramuscularly (into EDL muscles)/1, 3 and 6 unit/kg | Reduction of Cav3.2 expression, reduction of calcium release in EDL muscles | 74 |
| P2X3 | In vivo | Rat/Spinal ventral root transection model | BoNT/A/Subcutaneously/7 unit/kg | Inhibition of P2X3 receptor overexpression | 75 |
| P2X2 and P2X3 | Human (children and adolescents) | Human/Neurogenic detrusor overactivity | BoNT/A/Intramuscularly (into detrusor muscle)/12 unit/kg up to 300 unit | Reduction in expression of P2X2 and P2X3 receptors | 76 |
| P2X7 | In vivo | Rat/CCI model | BoNT/A/Subcutaneously/10 and 20 unit/kg | Reduction of P2X7 expression in spinal cord neurons | 58 |
| In vitro | Rat/LPS-activated microglial cells line | BoNT/A/0.1 nM | Reduction of P2X7 expression | ||
| NK-1 | In vivo | Rat/plantar incision model | BoNT/A/Intraplantary (2 unit) and intrathecally (0.5 unit) | Inhibition of NK-1 receptor overexpression in dorsal horn neurons | 77 |
| NK-1 | In vivo | Mouse/formalin-induced pain model and SNL model | BoNT/B/Intrathecally/0.5 unit | Reduction of NK1-R internalization in spinal dorsal horn neurons, cleavage of VAMP I/II in sensory afferents | 78 |
| AMPA | In vivo | Rat/formalin-induced pain model | BoNT/A/Peripherally (into the right foot)/3 and 6 unit/kg | Reduction of AMPA receptor expression and glutamate secretion in spinal dorsal horn neurons | 51 |
| AMPA (GluA1 subunit) | In vivo | Mouse/Carrageenan-induced pain model | BoNT/B/Intraplantary/1 unit | Reduction of pGluA1 expression in spinal dorsal horn neuron | 79 |
| µ opioid | In vivo | Mouse/SNL model | BoNT/A/Intraplantary/15 pg/paw | Enhancement of µ opioid receptor expression in spinal dorsal horn neurons | 60 |
ION-CCI: chronic constriction injury to the infraorbital nerve, EDL: extensor digitorum longus, CCI: chronic compression injury, SCI: spinal cord injury, SNL: spinal nerve ligation.