Founder of Health Rising and Phoenix Rising
Is the any doubt that being in pain heightens one's anxiety levels? What is there to be more anxious about, after all, than pain? It turns out that being anxious also increases pain - the two, for some reason, are inextricably linked together. It's not that anxiety is going to produce pain but if you're in pain, it will make it worse.
Several studies recently posted on the Pain Research Forum indicate progress is being made in understanding how and why pain and anxiety are so closely linked.
Studies have shown that activity of the prefrontal cortex - the part of the brain that determines, among many other things, how much relevance to give to pain signals - is reduced in chronic pain. The question is why and how.
Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety.
Wang G-Q, Cen C, Li C, Cao S, Wang N, Zhou Z, Liu X-mei, Xu Y, Tian N-X, Zhang Y, Wang J, Wang L-P, Wang Y Nat Commun. 2015; 6:7660.
In the first study Chinese researchers put lab animals in pain and then stopped the nerve signals travelling from different parts of their brains to the prefrontal cortex. They found that stopping the signals coming from the prelimbic cortex stopped both the animals pain and anxiety. Further investigations suggested that excitatory neurons played a key role. Behind the hyperactive excitatory neurons, they believe, however, probably lies bollixed inhibitory pain signals coming from GABAergic neurons.
Indeed an underactive pain inhibition pathways are believed to be primarily responsible for the pain in fibromyalgia. The brain doesn't just receive pain signals. It filter the signals - turning them down via inhibitory pain pathways or by reducing the activity of those pathways - turns the signal strength up.
This study suggested that the signals that produce pain and anxiety that swamp the brain in FM and other people in pain begin as far down as the prelimbic cortex of the brain.
Further work pinned down a key enzyme in this process called cell division protein kinase 5 (CDK5) which appropriately enough, plays an essential role in sensory pathways. Interestingly, blocking this enzyme in mice has been shown to reduce their "learned fear". Increasing it's activity increases the duration of"learned fear". The enzyme is also associated with several neurodegenerative diseases.
“The study moves us one step closer to understanding the interaction between pain and anxiety in the brain,” David Seminowicz, University of Maryland, Baltimore, US, and Marta Ceko, National Center for Complementary and Integrative Health, Bethesda, US
The next study, also by Chinese researchers, examined the anterior cingulate cortex (ACC)- a part of the brain that has been highlighted in both chronic fatigue syndrome and fibromyalgia studies. One part of the ACC is a sensory processing center that regulates signals going up and down the brain. Another part assesses the amount of effort needed to carry out a task. This part is connected to several areas on interest in ME/CFS and FM including the amygdala, nucleus accumbens, hypothalamus, and anterior insula. Studies suggest the ACC plays a major role in chronic pain and regulates anxiety as well.
This study found that glutamate release by neurons onto the ACC increased both pain and anxiety in laboratory animals. The researchers were able to determine that ion channels called hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels played a key role in this process.
HCN channels and currents in both pre- and postsynaptic terminals in the ACC and, importantly, in thalamic neurons that project to the ACC. Block of HCN channels in the ACC prevented pre-LTP and reversed established pre-LTP, indicating the channels are required for induction and maintenance of plasticity. That result suggests that HCN antagonists might selectively dampen pre-LTP and the behaviors it underlies.
In the new study, Zhuo and colleagues looked at a different kind of LTP, generated by increased glutamate release from presynaptic terminals onto pyramidal neurons of the ACC. Their results show that this presynaptic LTP (pre-LTP) is induced after nerve injury or inflammation, and contributes not only to pain, but also to anxiety in a mouse model of neuropathic pain.