Published: April 9th, 2019
Here we present a protocol to perform intracranial pharmacological experiments followed by pain behavior assays in rodents. This protocol allows researchers to deliver molecular and cellular targets in the brain, for pharmacologic agents in the treatment of pain.
Pain is a salient sensory experience with affective and cognitive dimensions. However, central mechanisms for pain remain poorly understood, hindering the development of effective therapeutics. Intracranial pharmacology presents an important tool for understanding the molecular and cellular mechanisms of pain in the brain, as well as for novel treatments. Here we present a protocol that integrates intracranial pharmacology with pain behavior testing. Specifically, we show how to infuse analgesic drugs into a select brain region, which may be responsible for pain modulation. Furthermore, to determine the effect of the candidate drug in the central nerve system, pain assays are performed after intracranial treatment. Our results demonstrate that intracranial administration of analgesic drugs in a targeted region can provide relief of pain in rodents. Thus, our protocol successfully demonstrates that intracranial pharmacology, combined with pain behavior testing, can be a powerful tool for the study of pain mechanisms in the brain.
The central nervous system is known to play a key role in pain regulation. For example, glutamate signaling in the brain has a regulatory role in the context of pain1,2. Hence, there is a need to study cellular and molecular signaling pathways in the brain with respect to pain. In addition, there is a need to understand if molecular targets in specific brain regions can be modified to treat pain. Current studies of pain in the brain rely on in vitro studies of electrophysiology in combination with systemic (intraperitoneal) delivery of pharmacological agents. In vitro studies have obvious def....
All procedures in this study were approved by the New York University School of Medicine Institutional Animal Care and Use Committee (IACUC) as consistent with the National Institute of Health (NIH) Guide for the Care and Use of Laboratory Animals.
1. Stereotaxic Cannula Implantation
As an example, we infused an AMPAkine into the PFC via cannulas (Figure 1). We also infused morphine systemically to assess the synergistic analgesic effects between AMPAkines and morphine. These results show that AMPAkines and morphine have an additive analgesic effect. It also shows that intracranial injections have the power to discover, at least in part, a mechanism for drug activation in the context of pain.
In this study, we have demonstrated that intracranial pharmacology is a powerful tool to study pain mechanisms and has potential as a therapeutic delivery system. In our protocol, we delivered AMPAkines directly into the PFC and found that by enhancing glutamate signaling in the PFC, AMPAkines provided pain relief. We were able to demonstrate this through the use of intracranial injections combined with intraperitoneal injections, with subsequent pain assays. Based on the evidence of pain-relieving effects, when AMPAkine.......
This work was supported by the National Institute of General Medical Sciences (GM102691, GM115384), National Institute of Neurological Disorders and Stroke (NS100065), (Bethesda, MD, USA) and the Anesthesia Research Fund of New York University Department of Anesthesiology (New York, NY, USA).....
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