CaMKIIbeta in Pain and Addiction

Despite numerous efforts for improvement, treatment of chronic pain remains inadequate and comes with major side effects like addiction, underscoring the critical need to identify innovative therapeutic targets for its treatment. Ca2+/calmodulin dependent protein kinase II (CaMKII) represents a promising target as previous studies show the involvement of CaMKII and one of its four isoforms, CaMKIIα, in chronic pain. This study delves into understanding CaMKIIβ in pain and opioid addiction. Looking to reveal if CaMKIIβ is involved in inflammatory and neuropathic pain, I studied the evoked pain behavior of CaMKIIβ global knockout mice (KO) following Complete Freund’s Adjuvant (CFA) injection and Spared Nerve Injury (SNI). In both models, chronic pain was absent in KO mice. Moreover, through biochemical analysis, I discovered that CaMKIIβ may be contributing to chronic pain through phosphorylation of a key regulator of pain, Transient Receptor Potential Vanilloid (TRPV1). Additionally, utilizing sensory neuron specific CaMKIIβ knockout mice I determined that nociceptor specific CaMKIIβ mediates both evoked and on-going spontaneous pain in both chronic inflammatory and neuropathic pain models. I employed hematopoietic stem cell transplantation to induce sickle cell in transgenic mice and discovered that CaMKIIβ mediates sickle cell disease (SCD) pain. In addition, I studied the contribution of CaMKIIβ to opioid induced hyperalgesia (OIH) and showed that mice lacking CaMKIIβ never develop hyperalgesia after chronic opioid administration. I utilized this model to also study morphine antinociceptive tolerance and dependence, where I discovered that CaMKIIβ contributes to both processes. Overall, this work explores the role of CaMKIIβ in chronic inflammatory and neuropathic pain as well as SCD associated pain and OIH. It uncovers the involvement of CaMKIIβ in opioid addiction. This marks CaMKIIβ as a novel target that can be investigated further for development of new effective therapeutic agents against pain and opioid addiction.

Author dc:creator

• Giokdjen Ilktach (19841195)

• Health Sciences, Pharmacology
• Biology, Molecular
• Biology, Neuroscience

Statement dc:rights

• In Copyright
• Open Access after 2031-05-01

DOI dc:identifier

https://doi.org/10.25417/uic.32995709.v1

OAI identifier oai:identifier

oai:figshare.com:article/32995709