Chronic pain and the PAG 2022

Inspired by Xu et al 2022.[1]

Photo by TBS 44 on Unsplash.

PAG – periaqueductal gray
FC – functional connectivity
MRI – magnetic resonance imaging
fMRI – functional magnetic resonance imaging
CNSP – chronic neck and shoulder pain
HC – healthy control
MA – manual acupuncture
MC – metacarpal
BOLD – blood oxygen level dependant
pIns – posterior insula
PCS – pain catastrophising scale

key to acronyms

This paper came out a couple of weeks ago, but I could not access the full paper immediately, so I had to wait a week to highlight it. I was attracted by the mention of the PAG in the title since this is a key site in the neurophysiological mechanisms of acupuncture.

The study appears to be a collaboration between two centres in China and one in Canada – McMaster University. The two centres in China are Xi’an and a nearby city called Xianyang. Both are ancient cities, but the latter is now merged into the Xi’an metropolitan area. The first author of the paper has affiliations to both McMaster and Jiaotong University in Xi’an. Jiaotong University is one of the 9 most prestigious and well-funded universities in China – one of the so-called C9 League.

Now that we are happy with the origins of the paper, what is it about?

The full title includes the phrase functional connectivity (FC), which immediately implies there was a lot of time spent in MRI scanners. This is expensive and time-consuming so n=60 is a big number for such a study.

30 right-handed female patients with CNSP were recruited along with 30 pain-free healthy controls (HC) that were matched for age and sex. The CNSP group were scanned before and after a 4-week treatment period in which they each received 20 sessions of MA. The HC group where just scanned once and completed several psychometric outcome scales. The CNSP group completed the same scales plus symptom-related scales and functional indices both before and after the treatment course.

The points used were GB20, GB21, SI3, LU7, Jingtong, Jiantong and BL62. The paper includes a set of figures with point locations, so Jingtong appears to be one of the Baxie set of points, which are between the knuckles of the hands. It is indicated as the point between the ring and little finger knuckles (MC heads). Jiantong is about 4 cun below GB34, just anterior to the fibula, probably in peroneus longus or extensor digitorum longus. It is curious that I cannot find either of these points mentioned in my various online resources of traditional points. From my perspective the first 2 points on the list are probably the most important. BL10 is also in the diagrams but not listed in the text, so that may have been used as well.

Research on acupuncture using fMRI has been carried out for over 20 years, with the key early research coming from the late Kathleen Hui from Harvard.[2] As the technology advanced resolution improved and analysis of the measured activity was refined. So, we moved from simply watching large areas of the brain lighting up (increasing BOLD signal) to analysing simultaneous changes in either direction in smaller brain areas.

I have been waiting to see functional imaging of the brain stem, and I think this might be the first such paper in the acupuncture field. The research group were able to target an area of 3mm diameter in the right ventral PAG. This is called a seed-region approach, and it measures activity in the small region compared with other regions of the brain. In this case they measured activity in the PAG seed compared with all activity in the rest of the brain.

Functional connectivity increased between the PAG and the posterior insula

When compared with the HC group, the patients with CNSP had decreased FC between the PAG seed and 7 other brain regions, but only one region increased significantly in FC with the PAG following acupuncture treatment, and that was the posterior insula (pIns). This increase in FC between these two brain regions correlated with a decrease in pain catastrophising on the PCS.

As far as I am aware the pIns has a body homunculus for interoception, so it makes sense that increased activity here driving inhibition via the PAG could result in a reduced perception of suffering with CNSP, and thus improved or normalised FC means a lower level of pain and suffering related to incoming bodily sensations.


1          Xu H, Chen Y, Tao Y, et al. Modulation effect of acupuncture treatment on chronic neck and shoulder pain in female patients: Evidence from periaqueductal gray-based functional connectivity. CNS Neurosci Ther Published Online First: 19 January 2022. doi:10.1111/cns.13803

2          Hui KK, Liu J, Makris N, et al. Acupuncture modulates the limbic system and subcortical gray structures of the human brain: evidence from fMRI studies in normal subjects. Hum Brain Mapp 2000;9:13–25. doi:10.1002/(sici)1097-0193(2000)9:1<13::aid-hbm2>;2-f

Declaration of interests MC