intracranial-pharmacotherapy-and-pain-assays-in-rodents

Intracranial Pharmacotherapy and Pain Assays in Rodents

Pain is a salient sensory experience with affective and cognitive dimensions. However, central mechanisms for pain remain poorly understood, hindering the ...

New York University School of Medicine

Traditional methods to assess pain in rodents depend on measures of nociceptive responses, most commonly from the hind paws. While these measures can quantify nociceptive responses to allow pharmacologic testing, they typically have high inter-experimenter variability and are not time-sensitive enough to correct with neural processes that occur on millisecond scales.

A new automated device for quantifying mechanical nociceptive responses.

Pain is a complex sensory and affective experience. The current definition for pain relies on verbal reports in clinical settings and behavioral assays in animal models. These definitions can be subjective and do not take into consideration signals in the neural system. Local field potentials (LFPs) represent summed electrical currents from multiple neurons in a defined brain area. Although single neuronal spike activity has been shown to modulate the acute pain, it is not yet clear how ensemble activities in the form of LFPs can be used to decode the precise timing and intensity of pain. The anterior cingulate cortex (ACC) is known to play a role in the affective-aversive component of pain in human and animal studies. Few studies, however, have examined how neural activities in the ACC can be used to interpret or predict acute noxious inputs. Here, we recorded in vivo extracellular activity in the ACC from freely behaving rats after stimulus with non-noxious, low-intensity noxious, and high-intensity noxious stimuli, both in the absence and chronic pain. Using a supervised machine learning classifier with selected LFP features, we predicted the intensity and the onset of acute nociceptive signals with high degree of precision. These results suggest the potential to use LFPs to decode acute pain.

Local field potential decoding of the onset and intensity of acute pain in rats.

Chronic pain is known to induce an amplified aversive reaction to peripheral nociceptive inputs. This enhanced affective response constitutes a key pathologic feature of chronic pain syndromes such as fibromyalgia. However, the neural mechanisms that underlie this important aspect of pain processing remain poorly understood, hindering the development of treatments. Here, we show that a single dose of ketamine can produce a persistent reduction in the aversive response to noxious stimuli in rodent chronic pain models, long after the termination of its anti-nociceptive effects. Furthermore, we demonstrated that this anti-aversive property is mediated by prolonged suppression of the hyperactivity of neurons in the anterior cingulate cortex (ACC), a brain region well known to regulate pain affect. Therefore, our results indicate that it is feasible to dissociate the affective from the sensory component of pain, and demonstrate the potential for low-dose ketamine to be an important therapy for chronic pain syndromes.

Article	Year
A new automated device for quantifying mechanical nociceptive responses. Journal of neuroscience methods\| PubMed ID: 30521828	2019
Local field potential decoding of the onset and intensity of acute pain in rats. Scientific reports\| PubMed ID: 29844576	2018
Ketamine reduces aversion in rodent pain models by suppressing hyperactivity of the anterior cingulate cortex. Nature communications\| PubMed ID: 30218052	2018

Haocheng Zhou

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