Interleukin-1β overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents

Abstract

BackgroundChronic pain is often accompanied by short-term memory deficit and depression. Currently, it is believed that short-term memory deficit and depression are consequences of chronic pain. Here, we test the hypothesis that the symptoms might be caused by overproduction of interleukin-1beta (IL-1β) in the injured nerve independent of neuropathic pain following spared nerve injury in rats and mice.ResultsMechanical allodynia, a behavioral sign of neuropathic pain, was not correlated with short-term memory deficit and depressive behavior in spared nerve injury rats. Spared nerve injury upregulated IL-1β in the injured sciatic nerve, plasma, and the regions in central nervous system closely associated with pain, memory and emotion, including spinal dorsal horn, hippocampus, prefrontal cortex, nucleus accumbens, and amygdala. Importantly, the spared nerve injury-induced memory deficits, depressive, and pain behaviors were substantially prevented by peri-sciatic administration of IL-1β neutralizing antibody in rats or deletion of IL-1 receptor type 1 in mice. Furthermore, the behavioral abnormalities induced by spared nerve injury were mimicked in naïve rats by repetitive intravenous injection of re combinant rat IL-1β (rrIL-1β) at a pathological concentration as determined from spared nerve injury rats. In addition, microglia were activated by both spared nerve injury and intravenous injection of rrIL-1β and the effect of spared nerve injury was substantially reversed by peri-sciatic administration of anti-IL-1β.ConclusionsNeuropathic pain was not necessary for the development of cognitive and emotional disorders, while the overproduction of IL-1β in the injured sciatic nerve following peripheral nerve injury may be a common mechanism underlying the generation of neuropathic pain, memory deficit, and depression.

Brain-derived neurotrophic factor-TrkB signaling in the medial prefrontal cortex plays a role in the anhedonia-like phenotype after spared nerve injury

“…The previous clinical studies demonstrated that the incidence of comorbid chronic pain and depression is around 30-50% [1,4,5], which is in line with the present study. In this study, we found that rats with or without anhedonia-like phenotypes showed similar mechanical withdrawal thresholds, suggesting that the alterations in mood-related behaviors were independent of the degree of nociceptive damage, consistent with the previous studies [8,31,[38][39][40].…”

Anti-inflammatory efficiency of erythropoietin in sciatic nerve damage

“…These markers cause neuroinflammationdependent cascade to start and worsen things after nerve damage. This process is paused through anti-inflammatory activity [22,5]. Taking experimental studies as a reference, TNF-α and IL-1β were used to evaluate neuroinflammatory cascade in our study, and a significant increase was observed in the trauma group compared to the control group.It cannot be disregarded that myelinization is an important factor in recovery after nerve damage.…”

“…IL-1β and TNF-α are important cytokines which are released from glial cells, and they play a key role in chronic pain, memory and damage pathogenesis. It was observed that sciatic nerve damage in the environment increased starting from the fifth hour following nerve damage [5,6,3]. Cytokines such as IL-1β and TNF-α were used to determine the anti-inflammatory effect in different experimental models.…”

“…Impulse cannot be transmitted to the muscle or sensory organs stimulated by the damaged nerve cell, and a neurological dysfunction develops depending on the affected area [4].Disruption of blood flow due to crushing over the nerve and the presence of reperfusion after the restoration of the damage causes the formation of acute phase reactants (cytokines such as TNF-α and IL-1β) and free oxygen radicals. Furthermore, these cytokines that form in the neuro-inflammation cascade intensify the damage and result in myelin phagocytosis and the prevention of regeneration in damaged nerve cell [5,6].Although the efficiency of neurotrophic drugs, steroids, hormones, low dose radiation and different chemical materials in increasing nerve regeneration is reported today, and the highest level is technically reached in nerve repair with the development of microsurgical techniques, a total recovery cannot be provided in motor and sensory terms in nerve regeneration [1][2][3]7,8]. The peripheral nervous system is more successful in axonal regeneration as inhibitor myelin proteins are less dominant and Schwann cells are more active in distal.…”

Food-Derived Natural Compounds for Pain Relief in Neuropathic Pain

“…In a neuropathic pain model, IL-1 β expression is upregulated in the injured sciatic nerve, DRG, and spinal cord [39–41]. Interestingly, the injection of an IL-1 β -neutralizing antibody was shown to alleviate the behavior related to neuropathic pain [40].…”