September and August 2024 Pain Journal
I love reading research on chronic pain because it shows me how much progress we’re making in being able to successfully treat it. The amount of progress we’re making is changing the lives of those who live with pain every day. Here are some of the newest updates in pain research.
Takeaways:
- When having cancer treated with chemotherapy, patients may develop a pain condition known as chemo induced peripheral neuropathy. Researchers are learning how to replicate this condition in cells in a lab so they can study how to more effectively treat this condition.
- When it comes to pain education, there are four themes that seem to help people with chronic pain the most: validation of pain, separation of pain and pathology, influence of thoughts and feelings, knowing that pain can improve over time.
- Physical activity can improve pain tolerance over time.
- Botulinum neurotoxin (aka Botox) can be used to treat some types of neuropathic pain such as diabetic neuropathy, trigeminal neuralgia, poststroke pain, etc.
- A study showed that cognitive behavioral therapy can be used to significantly reduce pain in those with interstitial cystitis/chronic bladder pain.
- Virtual reality can be used to significantly decrease lower back pain.
Chemotherapy induced peripheral neuropathy models constructed from human induced pluripotent stem cells and directly converted cells: a systematic review
- Chemo Induced peripheral neuropathy (CIPN) is a common long-term side effect of chemotherapy
- Can occur in up to 85% of patients depending on the type of chemotherapy used and the dose
- Commonly leads to dose reduction or discontinuation of that specific chemo
- There is expected to be an increase in CIPN due to an increase in cancer survival rates
- Research has been limited to animal studies
- This study was a systematic review of 26 studies that reprogrammed human cells to model CIPN
- Study provided insights on how to conduct better studies on this topic
Smulders, Pascal S.H.a; Heikamp, Kima; Hermanides, Jeroena; Hollmann, Markus W.a,*; ten Hoope, Wernera,b; Weber, Nina C.a. Chemotherapy-induced peripheral neuropathy models constructed from human induced pluripotent stem cells and directly converted cells: a systematic review. PAIN 165(9):p 1914-1925, September 2024. | DOI: 10.1097/j.pain.0000000000003193
“I wish I knew what I know now”- pain science education concepts important for female persistent pelvic pain: a reflexive thematic analysis
- Persistent pelvic pain is an umbrella term for conditions w/ symptoms that impact gynecological regions, the lower urinary tract, the bowels and may cause sexual and pelvic floor dysfunction
- The cause is often unclear but it is believed that biological, psychological, and sociological factors contribute to pain
- A lot of guidelines recommend surgical and medical management, but these often result in very little pain reduction
- For example, 20-40% of people who undergo laparoscopic surgeries for endometriosis have the same or worsened pain after the surgery and up to 50% require repeat surgeries.
- Guidelines rarely address psychosocial contributions to treating pelvic pain which may explain why people have poor clinical outcomes
- Pain education is a critical component of pain management; it reconceptualizes peoples’ understandings about how pain works and provides a rationale for treatment that takes a more biopsychosocial approach
- Recommended as a first line intervention for persistent pain
- The benefits of pain education increase when combined with active and functional goal-directed strategies
- In one clinical trial, pain education was done in conjunction with pelvic floor physiotherapy
- Resulted in a decrease in pain that was more significant than physiotherapy done alone
- Improvements in pain intensity, coping, catastrophizing, and other symptoms
- This study was done to gain a better understanding of which concepts in pain education helps patients the most
- Participants talked about the four themes that helped them the most:
- Validation of pain: learning about the biological mechanisms of pain validates their pain as real. This is especially important if they have often felt dismissed by healthcare providers. This helps reduce self-blame.
- Separation of pain and pathology: It was helpful for participants to understand that pain does not always indicate pelvic damage. This knowledge was reassuring, especially for those with endometriosis.
- Influence of thoughts and feelings: Understanding that pain is influenced by psychological and social factors was empowering because it implies that they have some control over their pain. Participants emphasized the need for practical strategies for addressing thoughts and feelings.
- Pain can improve over time: Learning about the bioplasticity of the pain system, or its ability to change, gave participants a sense of hope and control. Metaphors such as “rewiring the brain” helped them grasp this concept.
Mardon, Amelia K.a,b; Chalmers, K. Janea,b; Heathcote, Lauren C.b,c; Curtis, Lee-Annea; Freedman, Lesleyd; Malani, Rinklee; Parker, Romyb,f; Neumann, Patricia B.a; Moseley, G. Lorimera,b; Leake, Hayley B.a,b,*. “I wish I knew then what I know now” — pain science education concepts important for female persistent pelvic pain: a reflexive thematic analysis. PAIN 165(9):p 1990-2001, September 2024. | DOI: 10.1097/j.pain.0000000000003205
Small fibre neuropathy frequently underlies the painful long-Covid syndrome
- 10-20% of people previously infected with covid may develop long-Covid syndrome which is characterized by a range of physical and mental health symptoms, including fatigue, brain fog, anxiety, depression, sensory symptoms, and pain
- Some people have developed neuropathic pain which may be triggered by an increase in proinflammatory cytokines, direct viral neuroinvasion, or an inflammatory autoimmune response
- This specific type of neuropathic pain is known as small fibre neuropathy
- Pain primarily affects distal regions and is associated w/ autonomic symptoms like orthostatic intolerance
Falco, Pietroa; Litewczuk, Daniela; Di Stefano, Giuliaa; Galosi, Eleonoraa; Leone, Caterinaa; De Stefano, Gianfrancoa; Di Pietro, Giuseppea; Tramontana, Lorenzoa; Ciardi, Maria Rosab; Pasculli, Patriziab; Zingaropoli, Maria Antonellab; Arendt-Nielsen, Larsc,d,e; Truini, Andreaa,*. Small fibre neuropathy frequently underlies the painful long-COVID syndrome. PAIN 165(9):p 2002-2010, September 2024. | DOI: 10.1097/j.pain.0000000000003259
Does pain tolerance mediate the effect of physical activity on chronic pain in the general population?
- This study examined the relationship between physical activity, cold tolerance, and chronic pain risk; it also looked at variations based on sex
- Women tend to have lower cold pain tolerance and higher rates of chronic pain
- Findings:
- Higher levels of long-term physical activity at baseline were associated w/ a lower risk of developing chronic pain. It even more specifically lowered the risk of developing moderate-to-severe chronic pain.
- Physical activity can improve pain tolerance overtime
Årnes, Anders Pedersena,b,*; Fjeld, Mats Kirkebyc,d; Stigum, Heine; Nielsen, Christopher Sivertc,f; Stubhaug, Audund,f; Johansen, Aslaka,g; Hopstock, Laila Arnesdatterh; Morseth, Bentei; Wilsgaard, Tomb; Steingrímsdóttir, Ólöf Annac. Does pain tolerance mediate the effect of physical activity on chronic pain in the general population? The Tromsø Study. PAIN 165(9):p 2011-2023, September 2024. | DOI: 10.1097/j.pain.0000000000003209
Characterizing the opioidergic mechanisms of repetitive transcranial magnetic stimulation-induced analgesia: a randomized control trial
- Repetitive transcranial magnetic stimulation (rTMS) is an emerging therapy for chronic pain treatment
- rTMS can target different parts of the brain. Targeting the primary motor cortex has reduced neuropathic pain and targeting the dorsolateral prefrontal cortex has reduced pain in fibromyalgia.
- There is only a small-to-medium response rate.
- This study was done to give us a better understanding of how rTMS reduces pain:
- When rTMS targets the prefrontal motor cortex, endogenous opioids are released
- When the dorsolateral prefrontal cortex is being targeted by rTMS, larger doses are needed for pain relief to occur
- The findings of this study ruled out placebo effects
Liu, Yinga; Sun, Junfenga; Wu, Chaomina; Ren, Jinxuana; He, Yannia; Sun, Naa; Huang, Haoa; Chen, QunShana; Liu, Dana; Huang, Yangyuxina; Xu, Fengb; Yu, Linaa; Fitzgibbon, Bernadette M.c,d; Cash, Robin F. H.e,f; Fitzgerald, Paul B.c; Yan, Mina,*; Che, Xianweig. Characterizing the opioidergic mechanisms of repetitive transcranial magnetic stimulation–induced analgesia: a randomized controlled trial. PAIN 165(9):p 2035-2043, September 2024. | DOI: 10.1097/j.pain.0000000000003220
Effects of Commonly Used Analgesics on sleep architecture: a topical review
- Sleep has a bidirectional relationship with pain; pain disrupts sleep and poor sleep leads to the worsening of pain
- Anxiety, fear, and worry are also associated with poor sleep problems
- Sleep problems are reported by ⅔ of pain clinic patients
- Sleep functions to promote homeostasis of both body and mind
- Poor sleep impacts the immune system, metabolic, cardiovascular, cognitive functions, and emotional regulation
- Sleep is regulated by two main processes: the circadian rhythm (controlled by the suprachiasmatic nucleus) and a homeostatic process that builds sleep pressure during wakefulness
- The circadian rhythm follows a 24 hour cycle; disrupting this rhythm can lead to sleep problems
- The homeostatic process ensures that extended wakefulness is followed by deep restorative sleep, especially N3 sleep where sleep pressure is relieved
- Mediators of sleep pressure include adenosine and the accumulation of wakefulness-related brain metabolites
- Sleep and the immune system are interconnected. Quality sleep promotes immune system function while poor sleep promotes inflammation.
- Proinflammatory cytokines can promote sleep which is why sleep increases during infection
- Sleep is crucial for plasticity, memory consolidation, and cognitive function
- REM sleep in particular aids in emotional regulation by protecting against amygdala overactivation
- Physiologic changes take place during sleep: heart rate, blood pressure, body temperature, and breathing decrease during NREM sleep, while REM sleep has irregular control of these functions
- Sleep disturbances can increase pain sensitivity, especially in women
- Sleep loss promotes a proinflammatory response, increases nociceptor sensitivity, affects the mesolimbic system
- The mesolimbic system regulates pain salience and the reward system
- Slow wave sleep (N3) is important for pain regulation; disrupting this sleep lowers pain thresholds
- Neuropathic pain leads to neuroinflammation and reduced N3 sleep
- A decrease in N2 sleep is linked to increased pain intensity in fibromyalgia patients
- The impact of REM sleep on pain is unclear
- Total sleep loss overtime is the primary contributor to pain hypersensitivity
- Different medications have different effects on sleep:
- Long-term use of opioids can cause sleep-disordered breathing and hypoxemia
- Certain antidepressants can increase and decrease certain phases in the sleep cycle
- The effectiveness of pain medications may be optimized by timing their administration according to circadian rhythms
Antila, Hannaa,b,c,*; Lilius, Tuomas O.c,d,e; Palada, Vinkob,f; Lohela, Terhic,g; Bell, Rae F.h; Porkka-Heiskanen, Tarjab; Kalso, Eijab,d,g. Effects of commonly used analgesics on sleep architecture: a topical review. PAIN 165(8):p 1664-1673, August 2024. | DOI: 10.1097/j.pain.0000000000003201
Peripheral and central neurobiological effects of botulinum toxin A (BoNT/A) in neuropathic pain: a systematic review
- Chronic neuropathic pain is challenging to treat due to maladaptive changes in the nociceptive system, leading to central sensitization and hyperexcitability of the central nervous system.
- The first line treatment is medications like gabapentin, tricyclic antidepressants, and SNRIs. Second line treatments include tramadol and a combination of first-line treatments. Third line treatments include SSRIs, anti-seizure drugs, NMDA antagonists, and interventional therapies.
- Botulinum neurotoxin has emerged as a second/third line treatment for neuropathic pain that is localized to one location.
- It has shown efficacy in conditions like diabetic neuropathy, postherpetic neuralgia, trigeminal neuralgia, poststroke pain, and spinal cord injuries. Some studies have shown pain reduction for up to 3 months. Some people have experienced a pain reduction by over 50%.
- This systematic review showed that botulinum neurotoxin has the potential to be used to treat several different chronic neuropathic pain conditions. Future research will work towards creating subtypes of botulinum toxin that will be more effective at reducing pain.
Moreau, Nathana; Korai, Sohaib Alib; Sepe, Giovannab; Panetsos, Fivosc; Papa, Micheleb; Cirillo, Giovannib,*. Peripheral and central neurobiological effects of botulinum toxin A (BoNT/A) in neuropathic pain: a systematic review. PAIN 165(8):p 1674-1688, August 2024. | DOI: 10.1097/j.pain.0000000000003204
A systematic review with meta-analyses of the association between stigma and chronic pain outcomes
- Stigma has been defined as a process where individuals are discredited or considered undesirable due to attributes or stereotypes
- There are four components of a stigma: labeling differences, linking labels to negative stereotypes, creating “us.v them” categories, subjecting the labeled individuals to discrimination and loss of status
- People with chronic pain experience stigmas. This may stem from a lack of visual explanation for pain, personal beliefs about pain, and evolutionary tendencies to associate pain with contagious diseases.
- For example, people with fibromyalgia (a condition with unclear medical causes) report higher levels of invalidation than those with rheumatoid arthritis
- Stigma can be internalized by individuals with chronic pain, potentially leading to worse outcomes
- This study was done to evaluate the connection between stigma and chronic pain
- Results:
- Addressing stigma may improve outcomes for chronic pain patients
- Stigma may be compounded by mental health conditions
- Stigma is prevalent among people with sickle cell disease
- Stigma should be addressed on institutional and societal levels. Efforts should focus on inclusive policies, empathy, and validation
Hickling, Lauren M.a,b; Allani, Selsebila; Cella, Matteoa,b; Scott, Whitneya,c,*. A systematic review with meta-analyses of the association between stigma and chronic pain outcomes. PAIN 165(8):p 1689-1701, August 2024. | DOI: 10.1097/j.pain.0000000000003243
A randomized controlled pilot trial of telemedicine delivered cognitive behavioral therapy tailored for interstitial cystitis/bladder pain syndrome
- Interstitial cystitis/bladder pain syndrome is a chronic pain condition resulting in debilitating urinary and pelvic pain, affecting millions of people in the United States
- Treatment options are limited. The only FDA approved drug for interstitial cystitis is Elmiron. This drug can have severe side effects such as vision loss.
- People with interstitial cystitis often experience a lot of distress and may experience anxiety, depression, and PTSD, which may exacerbate symptoms.
- The American Urological Association recommends combining behavioral, oral, and procedural interventions
- These guidelines lack evidence based support
- Stigma surrounding interstitial cystitis
- This study tested a patient-centered cognitive behavioral therapy (CBT) intervention, delivered via telehealth to increase accessibility. The intervention aimed to reduce genitourinary symptoms
- Results:
- Nearly 40% of participants experienced significant improvement after 8 weeks of treatment. Participants experienced reduced pain and urinary symptoms.
- Key mechanisms in this treatment process include an improvement in coping skills, personalized therapy, and strong therapeutic alliance.
- The participants in this study had interstitial cystitis for an average of 14 years
McKernan, Lindsey C.a,b,*; McGonigle, Treyc; Vandekar, Simon N.c; Crofford, Leslie J.d; Williams, David A.e; Clauw, Daniel J.e; Bruehl, Stephenf; Corbett, Blythe A.a; Dmochowski, Roger R.g; Walsh, Elizabeth G.b; Kelly, Anna Gracea,h; Sutherland, Susanna L.b; Connors, Erin L.f; Ryden, Annaa; Reynolds, William Stuartg. A randomized-controlled pilot trial of telemedicine-delivered cognitive-behavioral therapy tailored for interstitial cystitis/bladder pain syndrome. PAIN 165(8):p 1748-1760, August 2024. | DOI: 10.1097/j.pain.0000000000003188
The effects of virtual reality neuroscience-based therapy on clinical and neuroimaging outcomes in patients with chronic back pain: a randomized clinical trial
- Chronic musculoskeletal pain remains difficult to manage. This may be because there is a lack of focus on how cognitive and emotional processes in the brain drive chronic pain.
- Newer virtual reality (VR) based therapies can target chronic pain by changing cognitive and affective processes. These interventions emphasize the brain’s role in chronic pain, incorporating pain neuroscience education along with cognitive, behavioral, and emotional exercises in a virtual environment.
- This immersive approach aims to reduce maladaptive thoughts and emotions like catastrophizing and fear avoidance.
- Chronic pain is associated with brain changes involving networks related to sensory processing, reappraisal, and attention to pain. These brain changes may be reversed with successful treatments.
- This study tested Virtual Reality Neuroscience Based Therapy (VRNT) on patients with chronic back pain to see if it would reduce pain intensity, improve functioning, and alter brain connectivity patterns
- MRI scans were done before and after treatment
- Study was conducted during the pandemic
- Results:
- Significant reductions in pain intensity that lasted for the 2 week follow-up
- There were decreases in the fear of physical activity and pain catastrophizing
- There were improvements in quality of life, sleep, and fatigue
- Nearly half of the participants experienced 50% or greater reduction in pain. This means it outperformed cognitive behavioral therapy
- MRI scans before and after showed that there were changes within the brain such as increased functional connectivity
Čeko, Martaa,*; Baeuerle, Tassilob; Webster, Lynnc; Wager, Tor D.d; Lumley, Mark A.e. The effects of virtual reality neuroscience-based therapy on clinical and neuroimaging outcomes in patients with chronic back pain: a randomized clinical trial. PAIN 165(8):p 1860-1874, August 2024. | DOI: 10.1097/j.pain.0000000000003198
So interesting! Especially the relationship between general fitness and pain thresholds. It makes sense! Linda 🙂