Bilateral changes of TNF-α and IL-10 protein in the lumbar and cervical dorsal root ganglia following a unilateral chronic constriction injury of the sciatic nerve

Abstract

BackgroundThere is a growing body of evidence that unilateral nerve injury induces bilateral response, the mechanism of which is not exactly known. Because cytokines act as crucial signaling molecules for response of peripheral nerves to injury, they may be induced to mediate the reaction in remote structures.MethodsWe studied levels of tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) proteins using ELISA in the ipsilateral and contralateral lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) from naïve rats, rats operated on to create unilateral chronic constriction injury (CCI) of the sciatic nerve, and sham-operated rats. Withdrawal thresholds for mechanical allodynia and thermal hyperalgesia were measured in the ipsilateral and contralateral hind and forepaws.ResultsThe ipsilateral hind paws of all rats operated upon for CCI displayed decreased withdrawal thresholds for mechanical allodynia and thermal hyperalgesia, while no significant behavioral changes were found in the contralateral hind paws and both forepaws. Significantly lower baseline levels of TNF-α and IL-10 protein were measured by ELISA in the lumbar than cervical DRG of naïve rats. Bilateral elevation of TNF-α was induced in both the lumbar and cervical DRG by unilateral CCI of the sciatic nerve for 7 and 14 days, while the level of IL-10 protein was increased bilaterally in the lumbar DRG 1 and 3 days after operation. IL-10 levels declined bilaterally even below baseline level in both cervical and lumbar DRG 7 days from CCI and normalized after 14 days. In contrast to no significant changes in TNF-α, level of IL-10 protein was significantly increased in the ipsilateral lumbar DRG after 3 days and bilaterally in the lumbar DRG after 14 days from sham operation.ConclusionsThe results of our experiments show a bilateral elevation of TNF-α and IL-10 not only in the homonymous DRG but also in the heteronymous DRG unassociated with the injured nerve. This suggests that bilaterally increased levels of TNF-α and IL-10 in DRG following unilateral CCI are linked with general neuroinflammatory reaction of the nervous system to injury rather than only to development and maintenance of neuropathic pain.

Intrathecal siRNA against Toll-like receptor 4 reduces nociception in a rat model of neuropathic pain

“…Sun T et al 43 also observed that the changes of mechanical and thermal pain thresholds and spinal TNF-α and IL-1β mRNA expression were isochronous, and effective suppression on CCI-induced up-regulation of TNF-β mRNA and IL-1α mRNA expression might be conducive to reduce mechanical allodynia and thermal hyperalgesia in neuropathic pain rats. These findings were coincident with the study of Jancálek R and so on 44-46. Thus, we believed that TNF-α and IL-1β might mediate the CCI-induced allodynia.…”

Assessment of Blood-Brain Barrier Function and the Neuroinflammatory Response in the Rat Brain by Using Cerebral Open Flow Microperfusion (cOFM)

“…5). This fact is supported by an earlier observation that IL-10 can suppress synthesis of proinflammatory cytokines, such as TNF-alpha, IL-6, and IL-1 by targeting circulating immune cells, liver, and spleen [56], [57], and can down-regulate receptors for proinflammatory cytokines [58]. We detected a slight increase in serum IL-10 as early as 1 h after LPS injection.…”

The importance of TRPV1-sensitisation factors for the development of neuropathic pain

“…2). Upregulation of TNFα transcription in DRG neurons is in the line with studies by Jancálek et al (2010) in experimental models of peripheral neuropathy. Furthermore, TRPV1 receptor sensitivity to endogenous and exogenous ligands may be modulated by TNFα pretreatment, resulting in increased nociceptive signal transmission (Khan et al, 2008;Spicarova and Palecek, 2009).…”