Nucleus pulposus-induced nerve root injury: effects of diclofenac and ketoprofen

Abstract

IntroductionSpinal nerve root injury can be induced by chronic compression and/or the presence of nucleus pulposus [1, 3, 4, 5,20,21,22,26,31,32,33,34,35,36,37,38,39,46,52]. It has been demonstrated experimentally that epidurally applied autologous nucleus pulposus, without any compression, can induce significant changes in nerve root morphology and function in animal models [4, 5,21,22,31,34,35]. Nucleus pulposus has been demonstrated to have inflammatogenic properties [33] and abundant macrophages and interleukin-1β immunoreactive cells have been demonstrated in human disc hernias, suggesting an active inflammation [11, 13]. Inflammatory mechanisms have been suggested to be of pathogenetic significance in sciatAbstract Main problem. Nucleus pulposus and/or chronic compression can induce spinal nerve root injury. Inflammation has been proposed as having major importance in the pathophysiologic mechanisms involved in the induction of such injuries. Corticosteroids, potent anti-inflammatory drugs, have been demonstrated to reduce nucleus pulposusinduced spinal nerve root injury. The aim of the present study was to assess the effects of two potent nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac and ketoprofen, in experimental nucleus pulposus-induced spinal nerve root injury in a pig model. Methods. Eighteen pigs were included in the study. Autologous nucleus pulposus was harvested from a lumbar disc and applied locally around the first sacral nerve root after a partial laminectomy of the first and second sacral vertebrae. Six pigs were treated with daily intramuscular injections of diclofenac, 3 mg/kg body weight, for 7 days. Six other pigs were treated with daily intramuscular injections of ketoprofen, 4 mg/kg body weight, for 7 days. As controls, six pigs received injections with physiologic saline. After 7 days, the pigs were reanesthetized and the nerve conduction velocity over the exposed nerve root area was determined. Results. The nerve conduction velocity was significantly higher in pigs treated with diclofenac than in the salinetreated controls, (57±6 m/s vs 38± 18 m/s, P<0.05, Student's t-test). The velocity in pigs treated with ketoprofen, 42±24 m/s, did not differ significantly from that of controls. Conclusions. This study of two potent NSAIDs indicates that nucleus pulposus-induced nerve root dysfunction may be reduced by diclofenac but not by ketoprofen. The reason for this difference is not known, but it might be related to the fact that ketoprofen and diclofenac belong to different NSAID subgroups and have a different selectivity for the two cyclo-oxygenases COX-1 and COX-2.

Anti-inflammatory Chitosan/Poly-γ-glutamic acid nanoparticles control inflammation while remodeling extracellular matrix in degenerated intervertebral disc

“…Df-NPs decreased IL-6, IL-8 and PGE 2 production, indicating that Df released from the NPs maintained its ability to inhibit COX-2 pathway, as expected [15], and similarly to what was observed with Df injection [32]. NPs, with and without Df, were shown to affect macrophage functional behavior in vitro, by stimulating the production of IL-6, IL-10, TNF-a but not IL-12/23, while PGE 2 was only stimulated by NPs without Df [17].…”

“…Df reduced nucleus pulposus-induced nerve root dysfunction after 7 days of treatment [15]. In the pro-inflammatory/ degenerated IVD ex vivo model previously established by us, Df injection down-regulated IL-6, IL-8 and decreased PGE 2 production, and also seemed to have an effect in IVD ECM remodeling by down-regulating MMP1, while up-regulating Agg expression [32].…”

“…These drugs affect the arachidonic acid cascade, inhibiting particularly the cyclo-oxygenase (COX) and lipoxygenase pathways, decreasing inflammation and pain [14,15], and have been widely used in osteoarticular disorders [16]. A local NSAIDsbased therapy would increase drug targeting and bioactivity, while minimizing drug bio-distribution through the organism and the risk of side effects [17].…”

Point of View

“…10,[12][13][14][15][16]29,30,36,52 Potential Clinical Relevance Previous investigations by Olmarker and other researchers 32,35,37,48,50,53,54 provided circumstantial evidence that the nerve root injury seen at disc herniation may not solely come from mechanical irritation, but may also be induced by NP tissue coming into contact with the nerve root or liberated substances that irritate the nerve. 10,[12][13][14][15][16]29,30,36,52 Potential Clinical Relevance Previous investigations by Olmarker and other researchers 32,35,37,48,50,53,54 provided circumstantial evidence that the nerve root injury seen at disc herniation may not solely come from mechanical irritation, but may also be induced by NP tissue coming into contact with the nerve root or liberated substances that irritate the nerve.…”

“…These results clearly demonstrated that the extruded disc tissue is chemically inflammatory active. 33,37,63 Firstly, unspecific by using nonspecific drugs (undesirable due to side effects). 13,38,[59][60][61][62] The level of TNF-␣ can be influenced by different pathways.…”