Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia

Abstract

BackgroundPain constitutes the major non motor syndrome in Parkinson's disease (PD) and includes neuropathic pain; however current drug therapies used to alleviate it have only limited efficacy. This is probably due to poor understanding of the mechanisms underlying it.AimsWe investigated a major class of trigeminal neuropathic pain, dynamic mechanical allodynia (DMA), in a rat model of PD and in which a bilateral 6-hydroxy dopamine (6-OHDA) injection was administered to produce a lesion of the nigrostriatal dopaminergic pathway.Results and discussionLesioned animals presented significant DMA in the orofacial area that occurred from 4 days to 5 weeks post-injury. To investigate a segmental implication in the neuropathic pain induced by dopamine depletion, the expression of the isoform gamma of the protein kinase C (PKCg) and phosphorylated extracellular signal-regulated kinases 1/2 (pERK1/2) was explored in the medullary dorsal horn (MDH). There was a high increase in PKCg expression in the III and IIi laminae of the MDH of lesioned-animals compared to shams. pERK1/2 expression was also significantly high in the ipsilateral MDH of lesioned rats in response to non-noxious tactile stimulus of the orofacial region. Since pERK1/2 is expressed only in response to nociceptive stimuli in the dorsal spinal horn, the current study demonstrates that non-noxious stimuli evoke allodynic response. Intraperitoneal and intracisternal administrations of bromocriptine, a dopamine 2 receptor (D2R) agonist, significantly decreased DMA compared to control rats injected with saline. These data demonstrate for the first time that nigrostriatal dopaminergic depletion produces trigeminal neuropathic pain that at least involves a segmental mechanism. In addition, bromocriptine was shown to have a remarkable analgesic effect on this neuropathic pain symptom.

Calpain-2 contributes to neuropathic pain following motor nerve injury via up-regulating interleukin-6 in DRG neurons

“…This is in line with the finding that injury to motor neurons produces neuropathic pain in rats, although the situation in postpoliomyelitis patients might be more complicated. Furthermore, pain also constitutes the major non motor syndrome in Parkinson's disease (PD) (Dieb et al, 2014;Pellaprat et al, 2014). In our recent work, we have found that L5-VRT up-regulates interleukin-6 (IL-6) in uninjured primary afferent system, and that the absence of IL-6 achieved by pre-treatment with IL-6 neutralizing antibody delays the induction of mechanical allodynia in bilateral hindpaws (Wei et al, 2013a).…”

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“…Nigrostriatal dopaminergic fibres have a crucial role in the onset of Parkinson's disease and RLS . Some of these fibres contain somatosensory fibres, and lesions in this pathway reveal deafferentation, which induces trigeminal pain . In summary, BMS patients may perceive burning pain largely by central mechanisms based on the impaired pain modulation.…”

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