The hindpaw formalin injection test (an acute pain behavior test) may be useful to highlight pain mechanisms relevant to patients in the clinic. In mice it elicits a biphasic response: the first, linked to stimulation of the primary sensory neuron; the later, associated with inflammation and central sensitization.
This model is used to analyze, in each phase, the role of specific channels as well as the effect of drugs targeting these channels. Acid-sensing ion channels (ASICs) regulate synaptic activity and play an important role in neurodegenerative and pain conditions. Prior injection of an ASIC1a inhibitor and antisense ASIC1a RNA has been shown to affect both phases of the test (Mazzuca et al. 2007).
Pain perception is thought to occur in the anterior cingulate cortex (ACC); human studies have reported that painful stimuli evokes activation of the ACC: the degree of which is correlated with the intensity of pain (Zhao et al 2018). Neurons in the ACC are activated in both acute and chronic pain states.
We analyzed ACC ASIC1 protein levels in a murine acute pain model using the formalin injection test.
Our results show a biphasic response to formalin. Pain behavior was accompanied by increased ACC ASIC1 levels contralateral to the injection site compared to ipsilateral, and greater than in controls.
This work highlights the influence of formalin induced pain on the expression of ASIC1 channels, which may constitute a potential therapeutic target of new pain therapies.