Modulation of Pain by Endocannabinoids in the Periphery

Activation of cannabinoid receptors using systemic treatments produces analgesia in a variety of experimental pain models, but these effects are hindered by sedation and motor impairment mediated by receptors in the central nervous system. Targeting the endocannabinoid system in the periphery can bypass these unwanted side effects while still producing analgesia in both acute and chronic pain states. This chapter discusses the different approaches to increasing peripheral endocannabinoid activity in experimental models of acute and chronic pain, including inflammatory pain, neuropathic pain, and sickle cell disease. We also explore how these treatments alter nociceptive activity in the peripheral nervous system

Cisplatin and the Mu Opioid Receptor Antagonist Methylnaltrexone Inhibit Neurite Growth in Cultured Trigeminal Neurons

https://openworks.mdanderson.org/sumexp23/1040/thumbnail.jp

ApoA-I binding protein (AIBP) decreases mechanical hypersensitivity after plantar incision in a rat model of post-operative pain

https://openworks.mdanderson.org/sumexp22/1090/thumbnail.jp

The anterior cingulate cortex and pain processing

The neural network that contributes to the suffering which accompanies persistent pain states involves a number of brain regions. Of primary interest is the contribution of the cingulate cortex in processing the affective component of pain. The purpose of this review is to summarize recent data obtained using novel behavioral paradigms in animals based on measuring escape and/or avoidance of a noxious stimulus. These paradigms have successfully been used to study the nature of the neuroanatomical and neurochemical contributions of the anterior cingulate cortex to higher order pain processing in rodents

FaDu Human Squamous Cell Carcinoma Induces Hyperexcitability of Primary Sensory Neurons

https://openworks.mdanderson.org/sumexp21/1219/thumbnail.jp

Pain Inhibition by Optogenetic Activation of Specific Anterior Cingulate Cortical Neurons

<div><p>Cumulative evidence from both humans and animals suggests that the anterior cingulate cortex (ACC) is important for pain-related perception, and thus a likely target for pain relief therapy. However, use of existing electrode based ACC stimulation has not significantly reduced pain, at least in part due to the lack of specificity and likely co-activation of both excitatory and inhibitory neurons. Herein, we report a dramatic reduction of pain behavior in transgenic mice by optogenetic stimulation of the inhibitory neural circuitry of the ACC expressing channelrhodopsin-2. Electrophysiological measurements confirmed that stimulation of ACC inhibitory neurons is associated with decreased neural activity in the ACC. Further, a distinct optogenetic stimulation intensity and frequency-dependent inhibition of spiking activity in the ACC was observed. Moreover, we confirmed specific electrophysiological responses from different neuronal units in the thalamus, in response to particular types of painful stimuli (i,e., formalin injection, pinch), which we found to be modulated by optogenetic control of the ACC inhibitory neurons. These results underscore the inhibition of the ACC as a clinical alternative in inhibiting chronic pain, and leads to a better understanding of the pain processing circuitry of the cingulate cortex.</p></div

<i>In-vivo</i> Electrophysiology of inhibition of ACC neurons by optogenetics.

<p>(a) Schematic showing the mechanism of post-synaptic silencing of excitatory neurons due to optogenetic-stimulation of inhibitory neurons in ACC. (b) Representative neuronal firing in ChR2 transgenic mouse without (left) and with (right) light stimulation for 250 ms. (c) Rate histogram of neuronal spikes with varying intensity of light stimulation in the ACC. (d) Rate histogram of neuronal spikes with varying frequencies of light stimulation in the ACC. (e) Intensity-dependent firing rate of neurons in the ACC. (f) Frequency-dependent firing rate of ACC neurons. Rebound activity of excitatory neurons after switching off the laser is encircled. *P < 0.05 vs. control (laser off).</p