Neurochemical plasticity in persistent inflammatory pain

Goal of the Study?

In this study, ¹ the authors try to understand the mechanisms involved in the peripheral and central sensitization associated with inflammatory pain. To do this, they used models of inflammation to examine the expression and internalization of the substance P receptor (SPR) in the spinal dorsal horn.

 

Why are they doing this study?

Chronic inflammation is responsible for various illnesses of which pain is paramount including arthritis, back pain and other joint disorders. To date, the neurochemical changes that occur within the spinal cord that contribute to the creation and continuance of inflammation are poorly understood. 

 

What was done?

The authors used four models of inflammation, which they produced by injecting the hind paw with formalin to look at acute pain, carrageenan to look at short-term pain and complete Freund’s adjuvant (CFA) to examine long-term pain. They also examined the neurochemical changes in an animal model of polyarthritis induced by CFA injection into the base of the rat’s tail. They then compared this data to past electro-physiological and behavioural data to examine and illustrate the changes in the amount and/or site of release of SPR from primary sensory neurons, the number and location of SPR expressing spinal neurons that are activated by this released Substance P (SP) and the populations of neurons showing up-regulation of the SPR.

 

What did they find?

They looked at three types of inflammatory pain: acute, short-term and long-term, to demonstrate how SPR internalization may show the role of ongoing sensory neuron input to acute and persistent pain states. Overall, they found a unique neurochemical signature that characterizes each type of inflammatory pain within the spinal cord.

Formalin injection to examine acute pain resulted in a two-phase response with early and short pain response, followed by a longer and more persistent pain. They found that there is ongoing sensory nerve input from C fibres and the release of SP in the spinal cord during both phases. Unlike formalin-induced inflammation, when carrageenan was injected as a way to examine short-term inflammatory pain, the researchers found that SPR internalization was observed early after injection. Still, no ongoing SPR internalization was seen 3 hours after injection. The researchers found that both short- and long-term pain is characterized by a lack of spontaneous SP release from primary afferents, as well as an increase in both the number and the location of SPR-IR spinal neurons that are triggered in response to stimuli. However, the major difference found between short- and long-term pain is that in the latter, there is up-regulation of SPR on neurons in the spinal cord that is not seen in other types of pain. They argue this may contribute to the central sensitization observed in long-term inflammatory pain. 

 

Why do these findings matter?

Understanding mechanisms of pain provide potential pathways for targeted treatment for patients impacted by different types of pain.