The science behind pain is amazing and learning about it can help you find the way to your healing journey. However, it can also be overwhelming and confusing a good chunk of the time. Listed below are some recent studies published by the International Association for the Study of Pain. Just in case you don’t have the time to read through all of the in-depth research, here are some bullet points summarizing all of this new and exciting information:

• A study showed that a substance known as hyaluronan may decrease pain when placed on the skin.

• People with mild traumatic brain injuries are at risk for developing chronic headaches. Knowing this will drive researchers to look into chronic headache prevention in people who have experienced mild traumatic brain injuries.

• People with chronic pain are more likely to experience anxiety, depression, and other negative emotions. They are also more likely to be sensitive to pain and touch. Research is leading us to understand how emotions, bodily sensations, and pain are all connected.

• People who are started on opioids and have primary care doctors are more likely to decrease their opioid use over time compared to people who do not have primary care doctors.

• Medications targeting substances in the body known as autotaxin and Lysophosphatidic acid may be able to reduce cancer growth and pain in patients with bone cancer.

• When people have social support, they feel pain less intensely.

Studies:

“A Novel Potential Strategy for the treatment of inflammatory and neuropathic pain”

• Our bodies produce a substance known as hyaluronan which has the potential to either reduce pain or increase pain, depending specifically on its size. When it’s big, it reduces pain. When it’s small, it increases pain.

• It works by targeting a receptor called CD44

• Hyaluronan interacts with estrogen which causes women to have increased pain.

• A study was done that involved placing hyaluronan on the skin

• They found that it only reduced pain in male participants

• They found that they could make it work in females by blocking a specific receptor or by removing the ovaries

Queme, Luis F.. A novel potential strategy for the treatment of inflammatory and neuropathic pain. PAIN 164(12):p 2625-2626, December 2023. | DOI: 10.1097/j.pain.0000000000003007 

“The prevalence of persistent post-traumatic headache in adult civilian traumatic brain injury: a systematic review and meta-analysis on the past 14 years”

• Every year 69 million people experience a traumatic brain injury (TBI)

• A common issue that occurs after TBIs is Persistent Post-Traumatic Headache (PTH)

• About 47.1% of people with TBI develop PTH and it occurs more commonly in people with mild TBIs compared to people with severe TBIs

Herrero Babiloni, Albertoa,b,*; Bouferguene, Yasmineb; Exposto, Fernando G.c,d; Beauregard, Roxanneb; Lavigne, Gilles J.b,e; Moana-Filho, Estephan J.f; Arbour, Carolineb,g. The prevalence of persistent post-traumatic headache in adult civilian traumatic brain injury: a systematic review and meta-analysis on the past 14 years. PAIN 164(12):p 2627-2641, December 2023. | DOI: 10.1097/j.pain.0000000000002949 

“Bodily maps of emotions and pain: tactile and hedonic sensitivity in healthy controls and patients experiencing chronic pain”

• Our emotions prepare us to respond to challenges and they activate different parts of the body to promote survival

• Emotions send signals that are linked to our physical sensations and our internal body state

• Pain is an emotional experience that is tied to our body’s warning system

• When we experience acute (sudden, short-term) pain, our body goes into a fight-or-flight response

• Pain has physical and emotional aspects regardless of how long it lasts

• More severe pain is linked to higher stress levels and can limit our ability to be more aware of and express our emotions

• Researchers want to understand the connections between emotions and pain so they used a technique called Bodily Sensation Maps (BSM)

• People mark on a human figure where they feel changes in bodily functions during specific emotional states

• Comparing emotional body maps with sensory maps used in pain evaluations can help us understand how our emotions, bodily sensations, and pain are interconnected

• Study findings:

• People with chronic pain are more sensitive to pain and touch compared to those without chronic pain.

• Those with complex regional pain syndrome felt more pain in their arms

• Those with low back pain felt more pain in the lower back area

• Those with fibromyalgia felt more pain all over

• Those with neuropathic pain felt the most pain in their feet

• People with chronic pain reported much higher levels of negative emotions such as depression, anxiety, fear, and anger

Ojala, Juhania,*; Suvilehto, Juulia T.b,c; Nummenmaa, Laurid,e,f; Kalso, Eijaa,g. Bodily maps of emotions and pain: tactile and hedonic sensitivity in healthy controls and patients experiencing chronic pain. PAIN 164(12):p 2665-2674, December 2023. | DOI: 10.1097/j.pain.0000000000003027 

“Longitudinal Dose Patterns among patients newly initiated on long-term opioid therapy in the United States, 2018-2019: an observational cohort study and time-series cluster analysis”

• In 2020, there were 91,799 drug overdose deaths in the U.S. with a significant increase from the last year

• 18% of these deaths involved prescription opioids

• Even when taken as prescribed, opioids can lead to tolerance and physical dependence

• Abruptly stopping or reducing the dosage can lead to mental health crises and emergency room visits

• There’s a lot of variation in how doctors prescribe opioids

• This study was done to understand the patterns in opioid dosage for people who were newly prescribed these medications for the long term

• Study results:

• The study showed that many people who were started on high dosages of opioids either reduced their dosages or were able to completely stop taking opioids.

• Those who were started on very high doses sometimes increased their dosage which has the potential to be dangerous

• People who had primary care doctors were more likely to decrease or stop their dosage over time.

Rikard, S. Michaela*; Nataraj, Nisha; Zhang, Kun; Strahan, Andrea E.; Mikosz, Christina A.; Guy, Gery P. Jr. Longitudinal dose patterns among patients newly initiated on long-term opioid therapy in the United States, 2018 to 2019: an observational cohort study and time-series cluster analysis. PAIN 164(12):p 2675-2683, December 2023. | DOI: 10.1097/j.pain.0000000000002994 

Exosome-associated lysophosphatidic acid signaling contributes to cancer pain

• 60% of patients with bone cancer experience severe chronic pain

• As the cancer grows in the bone, it makes nerve cells more sensitive

• Lysophosphatidic acid (LPA) is a type of fat that helps cancer cells grow and spread

• LPA does this by attaching to specific receptors on nerve cells and then it triggers signals that contribute to the feeling of pain

• It is produced by a substance called autotaxin (ATX) which is released by exosomes

• Exosomes also help cancer cells grow and spread and they promote the sensation of pain

• If we can find a way to interfere with LPA and exosomes, we may be able to reduce cancer pain without the use of opioids

• When exosomes are injected into mice, it makes them really sensitive to touch and heat

• Blocking ATX stops the pain from happening

• Cancer cells produce more ATX than non-cancer cells

• Blocking ATX can reduce pain and the growth of cancer cells

• Targeting ATX and LPA may ultimately lead to a reduction in pain and a slow down in the growth of cancer cells

Khasabova, Iryna A.a; Khasabov, Sergey G.a; Johns, Malcolma; Juliette, Joea; Zheng, Aunikaa; Morgan, Hannaha; Flippen, Alyssaa; Allen, Kajea; Golovko, Mikhail Y.b; Golovko, Svetlana A.b; Zhang, Weia,c; Marti, Jamesd; Cain, Davida; Seybold, Virginia S.d; Simone, Donald A.a,*. Exosome-associated lysophosphatidic acid signaling contributes to cancer pain. PAIN 164(12):p 2684-2695, December 2023. | DOI: 10.1097/j.pain.0000000000002967 

“Neuropilin-1 is essential for vascular endothelial growth factor A-mediated increase of sensory neuron activity and development of pain-like behaviors”

• In our bodies we have these proteins called neuropilins that help with guiding the growth of blood vessels and nerves

• These proteins play a role in pain when they pair up with another protein called vascular endothelial growth factor A (VEGFA)

• VEGFA increases pain in different situations such as nerve damage or diabetes

• Studies have shown that there is a connection between high levels of VEGFA and more severe pain in conditions like osteoarthritis and lower back pain

• Blocking neuropilin can reduce pain

• Understanding the connection between VEGFA and neuropilins may help us develop medications that target these proteins which can lead to a reduction in pain

• When VEGFA interacts with neuropilins it turns up the volume on pain

• There are different forms of VEGFA. Some forms increase pain and other forms decrease pain.

• After an injury, certain immune cells release VEGFA after an injury, making nerves more active and sensitive to pain

• There is currently a drug being tested on cancer patients that targets neuropilins and it seems to work well at reducing pain

Gomez, Kimberlya,b; Duran, Paza,b; Tonello, Raquela,b; Allen, Heather N.a,b; Boinon, Lisac; Calderon-Rivera, Aidaa,b; Loya-López, Santiagoa,b; Nelson, Tyler S.a,b; Ran, Dongzhic; Moutal, Aubind; Bunnett, Nigel W.a,b,e; Khanna, Rajesha,b,e,*. Neuropilin-1 is essential for vascular endothelial growth factor A–mediated increase of sensory neuron activity and development of pain-like behaviors. PAIN 164(12):p 2696-2710, December 2023. | DOI: 10.1097/j.pain.0000000000002970 

“The impact of the social context on the development of secondary hyperalgesia: an experimental study”

• Researchers are trying to understand why some people are more likely to experience persistent pain

• Research is showing that social context can influence how we experience pain

• Studies have shown that having social support tends to make pain less intense

• Feeling socially threatened can make pain worse

• Secondary hyperalgesia- increased sensitivity to pain around the original painful area

• This study involves inducing secondary hyperalgesia in volunteers and checking if having their partner holding their hand reduces sensitivity

• Study results:

• When people have social support, they feel pain less intensely

• People with higher levels of attachment anxiety felt less pain when they had social support

• People with high attachment avoidance (those who avoid getting too close in relationships) felt less pain overall, regardless of whether or not they had social support

• Suggests that they have found ways to handle pain on their own

Jaltare, Ketan Prafulla; Vanderijst, Laetitiaa; Karos, Kaib,c; Torta, Diana M.a,*. The impact of the social context on the development of secondary hyperalgesia: an experimental study. PAIN 164(12):p 2711-2724, December 2023. | DOI: 10.1097/j.pain.0000000000002971 

“Pubertal development and pain incidence and characteristics in children: a 1-year prospective cohort study of a national sample”

• Pain is pretty common among teenagers and it can last into adulthood

• A study was done to determine if different aspects of puberty play a role in how teenagers experience pain.

• Study findings:

• Girls who felt like they were going through puberty more quickly were more likely to experience pain

• Boys who felt like their puberty changes were not happening in sync (voice changes and hair growth) were more likely to have pain

• Boys who have higher levels of testosterone and DHEA had lower chances of developing pain

• Higher testosterone levels in girls was linked to having a higher chance of developing pain

Li, Ruia,*; Lopez, Daniel A.b; Gupta, Meenalc; Palermo, Tonya M.a,d. Pubertal development and pain incidence and characteristics in children: a 1-year prospective cohort study of a national sample. PAIN 164(12):p 2725-2736, December 2023. | DOI: 10.1097/j.pain.0000000000002969 

“Large-scale momentary brain co-activation patterns are associated with hyperalgesia and mediate focal neurochemistry and cross-network functional connectivity in fibromyalgia”

• Research shows that fibromyalgia is linked to changes in how the nervous system works

• Imbalances in pro-pain and anti-pain activity

• Disrupted communication between different brain networks

• This study was done to gain a better understanding of how the brain works in fibromyalgia

• Results:

• People with fibromyalgia showed increased sensitivity to pain during a cuff pressure test

• When experiencing prolonged periods of pain, certain patterns of brain activity were different between fibromyalgia patients and pain free individuals

• Higher excitatory neurotransmitter levels

• Pain influenced brain patterns related to attention and sensorimotor activity

• Brain networks that focus on attention and self-reflection are more connected in fibromyalgia patients than they are in healthy patients

• Fibromyalgia was compared to a “floodgate” of sensory information into the brain; overflow of information may explain why people w/ fibromyalgia don’t only experience sensitivity to pain, but also lights and sounds

Mawla, Ishtiaqa,b,*; Huang, Ziruic; Kaplan, Chelsea M.b; Ichesco, Ericb; Waller, Noaha,b; Larkin, Tony E.b; Zöllner, Helge J.d,e; Edden, Richard A.E.d,e; Harte, Steven E.a,b; Clauw, Daniel J.b; Mashour, George A.a,c; Napadow, Vitalyf,g; Harris, Richard E.a,b,h,i. Large-scale momentary brain co-activation patterns are associated with hyperalgesia and mediate focal neurochemistry and cross-network functional connectivity in fibromyalgia. PAIN 164(12):p 2737-2748, December 2023. | DOI: 10.1097/j.pain.0000000000002973 

“Perioperative insomnia trajectories and functional outcomes after total knee arthroplasty”

• This study is about people who undergo knee replacement surgery due to knee osteoarthritis

• Some people still have pain afterwards

• Factors that predict success are how severe the knee issues are, feelings of depression, and the use of strong painkillers- linked to poorer outcomes

• One factor that has not been studied is insomnia; specifically sleep before and after the procedure

• This study wants to understand how sleep right before and after surgery affects the long-term results

• Insomnia is common after knee replacement surgery; gets worse around 6 weeks after surgery and can stick around for several months

• Findings:

• Everyone experienced less pain after surgery, but those who had ongoing sleep problems had more pain than those who did not have sleep problems

• People who had trouble sleeping before and up to 6 weeks after the surgery continued to have sleep problems for 3-6 months after the surgery. By 6 months, their sleep usually improved.

• Those with persistent sleep problems had more difficulty with physical activity

• Those who who developed sleep problems had similar factors like higher anxiety, depression, and pain; they were more likely to use opioids

• Study suggests that treating sleep problems before surgery is crucial

• Addressing sleep problems early can help prevent chronic pain

Hamilton, Katrina R.a; Hughes, Abbey J.b,*; Campbell, Claudia M.a; Owens, Michael A.a; Pester, Bethany D.c; Meints, Samantha M.c; Taylor, Janiece L.d; Edwards, Robert R.c; Haythornthwaite, Jennifer A.a; Smith, Michael T.a. Perioperative insomnia trajectories and functional outcomes after total knee arthroplasty. PAIN 164(12):p 2769-2779, December 2023. | DOI: 10.1097/j.pain.0000000000002977 

“Mechanisms of education and graded sensorimotor retraining in people with chronic low back pain: a mediation analysis”

• Researchers created an approach called Resolve for treating chronic low back pain

• Combines education and graded sensorimotor retraining 

• Targets various factors: how we think about pain, changes in sensation and movement, and our perception of our own bodies

• Showed promising results in a recent study

• This study is being done to understand why and how Resolve works

• Results:

• They discovered that Resolve works well b/c it changed how people thought about their back pain, how much they worried about it, and how confident they felt in dealing with the pain

Cashin, Aidan G.a,b,*; Lee, Hopinc,d; Wand, Benedict M.e; Bagg, Matthew K.a,f,g; O’Hagan, Edel T.a,h; Rizzo, Rodrigo R.N.a,b; Stanton, Tasha R.i; Moseley, G. Lorimeri; McAuley, James H.a,b. Mechanisms of education and graded sensorimotor retraining in people with chronic low back pain: a mediation analysis. PAIN 164(12):p 2792-2800, December 2023. | DOI: 10.1097/j.pain.0000000000002978 

“Fear of progression, imagery, interpretation bias, and their relationship with endometriosis pain”

• Endometriosis effects 1 in 9 women; can cause pain, fatigue, and fertility issues

• People w/ endometriosis tend to fear that their pain will get worse with time; this could lead to more psychological distress and pain

• The researchers in this study looked at two factors:

• Interpretation bias- how people interpret their pain

• Mental imagery- the images that come to mind when thinking about their condition

• Findings:

• The fear of progression can make the impact of pain even worse, affecting daily life activities, work, relationships

• May cause them to avoid activities and seek out more health care options

• This fear of progression can ultimately make their pain harder to handle

Todd, Jemmaa,b,*; Pickup, Brydeea; Coutts-Bain, Daelina. Fear of progression, imagery, interpretation bias, and their relationship with endometriosis pain. PAIN 164(12):p 2839-2844, December 2023. | DOI: 10.1097/j.pain.0000000000003003