Pain MechanismBotulinum toxin type a (150 kDa) decreases exaggerated neurotransmitter release from trigeminal ganglion neurons and relieves neuropathy behaviors induced by infraorbital nerve constriction
Section snippets
Trigeminal neuropathy model
All procedures regarding animal usage in this study were performed in accordance to specifications of an animal protocol approved by Okayama University (OKU-2007137). All experiments were conformed to relevant National Institutes of Health guidelines on the ethical use of animals. We minimized the number of animals used and their suffering. The unilateral constriction of the infraorbital branch of the trigeminal nerve (IoN) was made according to the method described by Vos et al. (1994). Adult
In vitro pre-treatment with BoNT decreases KCl-evoked FM4-64 release from somata of acutely isolated TRG neurons
Initially we measured FM4-64 fluorescence intensity by confocal microscopy (2.0 s intervals) before and after KCl stimulation in acutely isolated neurons from naive rats with or without BoNT pre-treatment (BoNT/A was pre-applied in vitro for 3 h). We previously reported that the basal decay rate in FM4-64 intensity is dependent on the rate of signal acquisition (photobleaching) and on background vesicular release, which varies between IB4 (+) and IB4 (−) neurons (Matsuka et al., 2007). Since it
Discussion
In this study we demonstrated that unilateral IoNC results in long-lasting (>2 weeks) tactile allodynia in the region innervated by the IoN. This is consistent with previous demonstrations that chronic constriction injury of the IoN produces behavioral alterations indicative of trigeminal neuropathic pain (Vos et al 1994, Idanpaan-Heikkila and Guilbaud 1999, Kitagawa et al 2006, Shinoda et al 2007). It is widely acknowledged that persistent hyperexcitability of primary sensory neurons is a
Conclusions
Our data show that unilateral IoNC in rats produces long-lasting behaviors of neuropathy which are concomitant with increased transmitter release from somata of TRG neurons acutely isolated from the side of the injury. We also demonstrate that peripheral injection of BoNT/A alleviates the pain behaviors of IoNC and decreases the exaggerated neurotransmitter release from acutely isolated ipsilateral TRG neurons. The data add to our understanding of neuropathic pain mechanisms and suggest that
Acknowledgments
This study was supported by a grant from the Ministry of Education, Science and Culture of Japan (No. 18390512), Ryobi Teien Memorial Foundation and Japanese Association for Dental Science.
References (77)
- et al.
Trigeminal P2X3 receptor expression differs from dorsal root ganglion and is modulated by deep tissue inflammation
Pain
(2005) - et al.
A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man
Pain
(1988) - et al.
The expression of P2X3 purinoreceptors in sensory neurons: effects of axotomy and glial-derived neurotrophic factor
Mol Cell Neurosci
(1998) - et al.
Dynorphin A(1-8) immunoreactive cell bodies, dendrites and terminals are postsynaptic to calcitonin gene-related peptide primary afferent terminals in the monkey dorsal horn
Brain Res
(1989) - et al.
Subcutaneous administration of botulinum toxin A reduces formalin-induced pain
Pain
(2004) Sodium channels and mechanisms of neuropathic pain
J Pain
(2006)Neuropathic pain: emerging treatments
Br J Anaesth
(2008)Trigeminal neuralgia and related disorders
Neurol Clin
(1989)- et al.
Analysis of the unmyelinated primary sensory neurone projection through the dorsal columns of the rat spinal cord using transganglionic transport of the plant lectin Bandeiraea simplicifolia I-isolectin B4
J Neurol Sci
(2004) Spinal nerve ligation: what to blame for the pain and why
Pain
(2000)
Ca(2+)-dependent exocytosis in the somata of dorsal root ganglion neurons
Neuron
Pharmacological studies on a rat model of trigeminal neuropathic pain: baclofen, but not carbamazepine, morphine or tricyclic antidepressants, attenuates the allodynia-like behaviour
Pain
Presynaptic effects of botulinum toxin type a on the neuronally evoked response of albino and pigmented rabbit iris sphincter and dilator muscles
Jpn J Ophthalmol
Spontaneous discharge originates in the dorsal root ganglion at the onset of a painful peripheral neuropathy in the rat
Neurosci Lett
Clinical application of Clostridium botulinum type A neurotoxin purified by a simple procedure for patients with urinary incontinence caused by refractory destrusor overactivity
FEMS Immunol Med Microbiol
Effects of carbamazepine on morphine-induced behavioral sensitization in mice
Brain Res
Small primary sensory neurons innervating epidermis and viscera display differential phenotype in the adult rat
Neurosci Res
Antiallodynic efficacy of botulinum neurotoxin A in a model of neuropathic pain
Neuroscience
Botulinum neurotoxins and formalin-induced pain: central vs. peripheral effects in mice
Brain Res
The synaptic vesicle protein 2C mediates the uptake of botulinum neurotoxin A into phrenic nerves
FEBS Lett
Spontaneous release of immunoreactive neuropeptide Y from the central terminals of large diameter primary afferents of rats with peripheral nerve injury
Neuroscience
Concurrent release of ATP and substance P within guinea pig trigeminal ganglia in vivo
Brain Res
Two types of neurotransmitter release patterns in isolectin B4-positive and negative trigeminal ganglion neurons
Neuroscience
Fixed-diameter polyethylene cuffs applied to the rat sciatic nerve induce a painful neuropathy: ultrastructural morphometric analysis of axonal alterations
Pain
Fluoride-resistant acid phosphatase-containing neurones in dorsal root ganglia are separate from those containing substance P or somatostatin
Neuroscience
Inflammation-induced changes in primary afferent-evoked release of substance P within trigeminal ganglia in vivo
Brain Res
Clostridial neurotoxins: new tools for dissecting exocytosis
Trends Cell Biol
Cannabinoid receptors and pain
Prog Neurobiol
Trigeminal neuralgia: the role of self-sustaining discharge in the trigeminal ganglion
Pain
A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury
Pain
Signs of neuropathic pain depend on signals from injured nerve fibers in a rat model
Brain Res
P2X3 receptor mediates heat hyperalgesia in a rat model of trigeminal neuropathic pain
J Pain
Experimental peripheral neuropathy decreases the dose of substance P required to increase excitatory amino acid release in the CSF of the rat spinal cord
Neurosci Lett
Localization of P2X2 and P2X3 receptors in rat trigeminal ganglion neurons
Neuroscience
Alteration of the second branch of the trigeminal nerve activity following inferior alveolar nerve transection in rats
Pain
Capsaicin-evoked release of immunoreactive calcitonin gene-related peptide from rat trigeminal ganglion: evidence for intraganglionic neurotransmission
Pain
Immunohistochemical study of the P2X2 and P2X3 receptor subunits in rat and monkey sensory neurons and their central terminals
Neuropharmacology
Transganglionic transport and binding of the isolectin B4 from Griffonia simplicifolia I in rat primary sensory neurons
Neuroscience
Cited by (76)
Botulinum toxin A and neuropathic pain: An update
2023, ToxiconNew analgesic: Focus on botulinum toxin
2020, ToxiconNeuronal selectivity of botulinum neurotoxins
2020, ToxiconBotulinum toxin A and neuropathic pain
2020, Bulletin de l'Academie Nationale de Medecine