Department of Pharmacology of Pain

General description
The Department of Pharmacology of Pain is devoted to studying the initiation and maintenance of pain processes, with particular emphasis on neuropathic pain, which occurs after peripheral nerve injuries due to lesions, cancer, diabetes, multiple sclerosis, hypoxia. This type of pain cannot be relieved by typical painkillers, therefore it is often considered a disorder without prospect of significant improvement. Despite numerous clinical and experimental studies, the molecular mechanisms involved in the development of pain is still not fully understood.
The purpose of our research is to identify alterations in endogenous opioid system homeostasis, which seem to be an important factor in the development of chronic pain. An activation of endogenous analgesic systems in response to the nervous system damage triggers homeostatic mechanisms and in consequence leads to an excessive activity of pro-nociceptive systems. Our research aims to determine various pro-nociceptive peptide pathways which contribute to the development of neuropathy.
Studies using both gene expression profiling and protein analysis indicate that neuropathic pain involves strong activation of many neuronal genes as well as genes related to the immune cell response, including microglial activation. This is an important area of research because there is no data evaluating the efficacy of combined use of opioids and inhibitors of microglia or proinflammatory factors, such as IL-1beta, CCL2, CCL5, as well as blockers of intracellular signaling pathways NF-kB, ERK1/2 and p38MAPK, in the treatment of neuropathic pain. Our studies also involve the search for new targets which could be used to develop more effective treatments of diabetic neuropathy. The results of these experiments demonstrate that modulation of neuroimmunological pathways, by administration of pentoxifylline (an inhibitor of inflammatory cytokines), minocycline (p38MAPK inhibitor), parthenolide (NF-κB inhibitor), U0126 (ERK1/2 inhibitor), SB203580 (p38MAPK inhibitor) PD98059 (MAPKK inhibitor), attenuates the development of neuropathic pain but may also augment the efficacy of opioids. We hope that the results of our research would provide an experimental basis for future clinical use of combination therapy employing opioid analgesics and glial inhibitors or other substances modulating the synthesis or action of proinflammatory factors, in order to increase the analgesic efficacy of drugs in the treatment of neuropathic pain.

Research methods

The most important recent scientific discoveries

This paper clarifies attenuated efficacy of opioid drugs in the treatment of neuropathic pain by demonstrating the presence of MOP and KOP receptors and the absence of the opioid DOP receptor on microglial cells. This finding may explain why DOP receptor agonists are inefficient in the treatment of neuropathic pain, as opposed to the attenuated effects of drugs acting through the other two opioid receptors and indicates future directions for the search for novel analgesics.

It has been shown that pro-inflammatory cytokines derived from glial cells activated by the nervous system damage play an important role in the neurotoxic effects of dynorphin in the neuropathic pain model. Inhibition of this activity significantly attenuates adverse effects of dynorphin, which is one of the factors involved in the neuropathic pain development.

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