Highlights from

TOXINS 2019

International Neurotoxin Association (INA) annual meeting

Copenhagen 16-19 January 2019

Pain and sensory mechanisms

Prof. Cristina Tassorelli (University of Pavia, Italy) talked about primary headaches: cluster, tension-type headache, benign cough headache, and migraine.

Migraine is a complex disorder characterised by recurring attacks whose initiation depends on endogenous and exogenous factors. It is a disturbance of sensory processing involving the meninges, cortex, thalamus, hypothalamus, brainstem nuclei, and cranial pain pathways. There are endogenous factors involved such as hyperexcitability of the cortex. In addition, there is participation of exogenous factors: peripheral stress, dietary products, and environmental changes may also initiate migraine through activation of sensory afferents. There is also activation of the trigeminovascular afferent fibres of the trigeminal ganglion, release of neurotransmitters from peripheral nerve terminals of trigeminovascular afferents, and vasodilation of the meningeal vessels. Plasma extravasation and mast cell degranulation lead to secretion of other pro-inflammatory substances in the dura (neurogenic inflammation). Activation of neurons in the trigeminal nucleus caudalis and in brain regions are associated with pain perception.

Migraine-related disability

A severe migraine attack is as disabling as quadriplegia, schizophrenia, or dementia, Prof. Tassorelli emphasised. Migraine-related disability is high and so is headache medication overuse, as shown by the years of life lost because of the disease [1]. Migraine is the third cause of disability in individuals below the age of 50.

Prof. Tassorelli pointed out that the antinociceptive effect of onabotulinum toxin A is distinct from its neuromuscular activity. Its biochemical effect, cleavage of SNAP-25 to impair synaptic vesicle fusion and neurotransmitter release, is the same at both sensory and motor nerve terminals. The toxin may suppress peripheral sensitisation, thereby possibly inhibiting central sensitisation [2,3].

Onabotulinum toxin A blocks peripheral acetylcholine release at presynaptic cholinergic nerve terminals. The therapeutic benefit is muscle relaxation. Onabotulinum toxin A also blocks the release of neurotransmitters associated with the genesis of pain and reduces the cell surface expression of ion channels and sensory receptors. Its treatment benefit is pain reduction.

  1. GBD 2015 Neurological collaborator Group. Lancet Neurol. 2017 Nov;16(11):877-897.
  2. Aoki KR. Headache. 2003 Jul-Aug;43 Suppl 1:S9-15.
  3. Whitcup SM, et al. Ann N Y Acad Sci. 2014 Nov;1329:67-80.

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.