Duloxetine ameliorates the impairment of diffuse noxious inhibitory control in rat models of peripheral neuropathic pain and knee osteoarthritis pain

Introducing descending control of nociception: a measure of diffuse noxious inhibitory controls in conscious animals

“…Randall-Selitto pressure stimulus, von Frey filaments, Hargreaves heat withdrawal threshold) upon injection of an irritant (i.e. capsaicin, formalin) to a distant body region (11,12,32,37) despite the fact that direct spinal neuronal recordings are not made. DNIC are abolished in rats following spinalisation (14) or cervical block with lidocaine (6), and a lesion to the dorsolateral funiculus (DLF) ipsilateral to an electrophysiologically recorded WDR neuron was previously shown to abolish DNIC expression (34).…”

Developments in Understanding Diffuse Noxious Inhibitory Controls: Pharmacological Evidence from Pre-Clinical Research

“…In the SNL model of peripheral neuropathy citalopram and fluoxetine, both SSRIs, failed to restore DNIC, 3 but escitalopram (also SSRI) restored DCN in traumatic brain injury (TBI) model, however an effect of the latter was not abolished by systemically applied atipamezole. 10 Duloxetine, an serotonin noradrenaline reuptake inhibitor (SNRI), restored DCN expression in late stage OA and PSNL models, 16 as well as in a TBI model. 10 Interestingly, systemic reboxetine, a NRI, did not restore DCN in TBI animals, 10 but its local spinal application did restore DNIC in SNL animals.…”

“…Finally, other agents like celecoxib, a cyclooxygenase type 2 (COX2) inhibitor, given orally, did not restore DCN in PSNL nor in late stage OA rats. 16 Systemic pregabalin (an analgesic acting on voltage-gated calcium channels (VGCCs) inhibiting calcium currents and de facto the release of neurotransmitters) also failed to restore DNIC and DCN expression in the late stage OA model and in an injury model of peripheral neuropathy. 16,41 Precisely, noradrenergic mechanisms are essential for the proper functioning of the DNIC pathway.…”

“…16 Systemic pregabalin (an analgesic acting on voltage-gated calcium channels (VGCCs) inhibiting calcium currents and de facto the release of neurotransmitters) also failed to restore DNIC and DCN expression in the late stage OA model and in an injury model of peripheral neuropathy. 16,41 Precisely, noradrenergic mechanisms are essential for the proper functioning of the DNIC pathway. A clear investigative focus on the reciprocal connectivity of brainstem noradrenergic nuclei with respect to their functionality upon conditioning is crucial to delineate the hierarchy of nucleus contributions to this unique type of inhibitory control.…”

“…12 Atipamezole was also shown to abolish DNIC expression in the early stage of monoiodoacetate (MIA) model of osteoarthritis (OA). 13 Furthermore, intrathecal application of another α 2 -AR antagonist yohimbine, also potently abolished DCN expression in three independent behavioural studies [14][15][16] (Table 2).…”