October and November Pain Journal

More research on chronic pain! There’s a lot of great information here that can give you a better understanding of how pain works and how it should be treated. Feel free to message me if you have any questions!

Takeaways:

• For people with joint pain, if your pain is more nociplastic than nociceptive, surgery may not be as effective for reducing pain.
• There is a bidirectional relationship between sleep and pain.
• Higher doses of opioids are associated with increased risks of motor vehicle accidents and falls.
• Children are more likely to develop chronic pain after an injury if their parents have higher levels of anxiety and protectiveness.
• Having a high stress job with low reward increases the risk of developing chronic low back pain.
• Low dose naltrexone may be an effective way to decrease certain types of pain.

Pain after cancer: navigating the complexities and embracing psychological insights

• As cancer survival rates continue to improve, the number of survivors facing long term pain is expected to rise
• Certain types of cancer are associated with higher risks of long term pain:
  • Bone cancers (Ewing sarcoma and osteosarcoma)
• 26% of childhood cancer survivors develop long-term chronic pain
• It is likely that the psychosocial aspects of cancer contribute to the chronic pain

Heathcote, Lauren C.. Pain after cancer: navigating the complexities and embracing psychological insights. PAIN 165(11):p 2396-2397, November 2024. | DOI: 10.1097/j.pain.0000000000003285 

An attempt to identify nociceptive and nociplastic pain profiles using a clinical test for joint pain

• Chronic joint pain is typically managed by exercise-based therapy, pharmacological treatments, and surgical interventions- treatment focuses on the joint itself
• Recent studies have shown that sensitivity in the nervous system plays a crucial role
  • This sensitivity is influenced by peripheral, spinal, and central pain modulation systems
• Nociplastic pain is a type of pain characterized by altered pain processing without clear nerve damage or local injury
• Nociceptive pain is caused by damage or inflammation
• People with joint pain can experience both nociplastic and nociceptive pain
• For patients with knee osteoarthritis, studies show that 20% of patients continue to experience pain after joint replacement therapy
• Patients with localized joint related pain tend to benefit from surgery whereas patients with heightened central pain sensitivity see less improvement after surgery
• It is difficult to identify if a patient’s pain is nociplastic or nociceptive and complex assessments are often not feasible in busy clinical settings
• Randomized trial was done using lidocaine injections to determine who has nociplastic v. nociceptive pain:
  • Those with nociceptive pain experienced greater pain reduction than those with nociplastic pain
  • Those with nociplastic pain often exhibit characteristics such as hyperalgesia, fibromyalgia signs, and high PainDETECT scores

Hertel, Emmaa; Ciampi de Andrade, Danielb; Kjær-Staal Petersen, Kristiana,b,*. An attempt to identify nociceptive and nociplastic pain profiles using a clinical test for joint pain. PAIN 165(11):p 2398-2400, November 2024. | DOI: 10.1097/j.pain.0000000000003292 

Biomarkers of stress as mind-body intervention outcomes for chronic pain: an evaluation of constructs and accepted measurement

• Physiological stress mechanisms may play a role in maintaining chronic pain. These mechanisms include hypothalamic-pituitary-adrenal (HPA) axis, allostatic load, telomere attrition, and sympathetic nervous function; also oxidative stress and alterations in stress-related brain networks (limbic and fear networks)
• Mind-body interventions such as mindfulness may help normalize the stress response , reduce central sensitization, and improve pain related sensory, emotional, and cognitive processes
• Allostatic load (AL) reflects wear and tear on the nervous system due to prolonged stress, which is linked to poorer health outcomes
• Shortened telomeres are a mark of cellular aging and are also associated with chronic pain. Stress exposure and cortisol reactivity impair telomere length.
• Oxidative stress results from an imbalance of free radicals and antioxidants 
• Changes in the limbic system are associated with pain, memory, and stress responses
• Mind-body interventions, such as mindfulness, show potential in reducing these stress related mechanisms, but results vary

Nelson, Saraha,b,*; Mitcheson, Morgana; Nestor, Bridgeta,b; Bosquet Enlow, Michelleb,c; Borsook, Davidd. Biomarkers of stress as mind–body intervention outcomes for chronic pain: an evaluation of constructs and accepted measurement. PAIN 165(11):p 2403-2408, November 2024. | DOI: 10.1097/j.pain.0000000000003241 

Bruxism, temporomandibular disorders, and headache: a narrative review of correlations and casualties

• Temporomandibular disorders encompass a range of painful and nonpainful conditions that impact the temporomandibular joint, masticatory muscles, and surrounding structures
  • Symptoms usually include jaw pain, muscle tenderness, and noises during jaw movement
  • There are three categorizations: 1. Muscle pain (myalgia) 2. Joint disorders 3. TMD-related headaches
  • Usually effects adults that are 20-40 years of age and is more common in women
  • Risk factors include stress, somatization, and depression.
• Bruxism is a behavior characterized by repetitive or sustained jaw movements. There are two forms: sleep bruxism and awake bruxism
  • Awake bruxism involves clenching teeth
  • Sleep bruxism is linked to central nervous system arousal during sleep
    • Risk factors: alcohol, caffeine, tobacco, specific medications, and psychosocial factors
• Headache is either primary (not caused by another disorder) or secondary (caused by another disorder)
  • Primary headaches include migraine, tension type headaches, and trigeminal autonomic cephalgias
• More research is needed to determine if bruxism, TMD, and headaches are related

Voß, Leonie Carolinea; Basedau, Haukea; Svensson, Peterb; May, Arnea,*. Bruxism, temporomandibular disorders, and headache: a narrative review of correlations and causalities. PAIN 165(11):p 2409-2418, November 2024. | DOI: 10.1097/j.pain.0000000000003277 

A systematic literature review on patient reported outcome domains and measures in nonsurgical efficacy trials related to chronic pain associated with endometriosis: an urgent call to action

• Endometriosis affects 10% of women of reproductive age globally
• Chronic inflammatory condition causing chronic pelvic pain
• Symptoms include non cyclical pelvic pain, dysmenorrhea (painful periods), dyspareunia (pain during sexual intercourse)
• Diagnosis can take up to 7 to 9 years due to its complex symptoms and need for surgical confirmation
• Treatment (medical and surgical) fails in up to 50% of patients

Rosenberger, Daniela Constanzea; Mennicken, Emiliaa; Schmieg, Irisa; Medkour, Terkiab; Pechard, Marieb; Sachau, Julianec; Fuchtmann, Fabiana; Birch, Judyd; Schnabel, Kathrina; Vincent, Katye; Baron, Ralfc; Bouhassira, Didierb; Pogatzki-Zahn, Esther Miriama,*. A systematic literature review on patient-reported outcome domains and measures in nonsurgical efficacy trials related to chronic pain associated with endometriosis: an urgent call to action. PAIN 165(11):p 2419-2444, November 2024. | DOI: 10.1097/j.pain.0000000000003290 

The bidirectional relationship between sleep problems and chronic musculoskeletal pain: a systematic review with meta-analysis

• Sleep problems such as poor sleep, insomnia, and obstructive sleep apnea is prevalent in people with chronic musculoskeletal pain (CMP)
  • 75% experience sleep problems and 44% experience sleep disorders
• Sleep problems are linked to lower quality of life, worsened health, and increased depression
• Research shows that there is a bidirectional relationship between sleep and CMP
• It is recommended that there should be screenings for sleep problems within clinical practice

Runge, Nilsa,b,c,*; Ahmed, Ishtiaqa; Saueressig, Tobiasd; Perea, Julyae; Labie, Celinea,b; Mairesse, Olivierc,f; Nijs, Joa,g,h; Malfliet, Anneleena,g,i; Verschueren, Sabineb; Van Assche, Dieterb,j; de Vlam, Kurtj,k; Van Waeyenberg, Tyboa; Van Haute, Jellea; De Baets, Liesbeta. The bidirectional relationship between sleep problems and chronic musculoskeletal pain: a systematic review with meta-analysis. PAIN 165(11):p 2455-2467, November 2024. | DOI: 10.1097/j.pain.0000000000003279 

The associations of opioid and benzodiazepine prescriptions with injuries among US military service members

• 25% of US active duty service members were prescribed opioids in 2010, w/ even higher usage rates among veterans with chronic pain diagnoses
• Prescription opioids have been linked to increased risks of motor vehicle accidents, overdose, and accidental injuries
  • This risk is dose dependent, meaning the higher the dose, the higher the risk
• Opioid use among service members is often accompanied by medications for mental health such as benzodiazepines
• The use of both opioids and benzodiazepines increases the risk of overdose and other adverse events
• 17% of service members with injuries had opioid use and 3.5% of injury cases involved the use of benzodiazepines
• Higher opioid doses are strongly associated with vehicle accidents and falls

Kelber, Marija S.a,*; Smolenski, Derek J.a; Belsher, Bradley E.a,b; O’Gallagher, Kevina; Issa, Fuada; Stewart, Lindsay Thonsena; Evatt, Daniel P.a. The associations of opioid and benzodiazepine prescriptions with injuries among US military service members. PAIN 165(11):p e138-e144, November 2024. | DOI: 10.1097/j.pain.0000000000003264 

Who develops chronic pain after an acute lower limb injury? A longitudinal study of children and adolescents

• Injury is common in childhood, with one-third of children experiencing a fracture before the age of 17
• Most recover within a reasonable amount of time, but as many as 35% of children report ongoing pain 3 months after an injury, which can lead to chronic pain
  • This may affect their physical, emotional, mental, and social functioning
  • They may have poorer academic, vocational, and social outcomes
• Children with chronic pain or more likely to experience chronic pain in adulthood
• Parental factors contribute to the risk of chronic pain:
  • Parents being overprotective or overly distressed in regards to their child’s pain, increase the risk of chronic pain in their children
• Other risk factors include older age, adverse life events, and female sex
• This study looked at 118 children with acute lower limb injuries aimed at identifying biopsychosocial risk factors for developing chronic pain:
  • Higher levels of child depression and fear of pain predicted the onset of chronic pain at three months
  • Higher parental protectiveness was linked to greater pain interference
  • Poorer child sleep, higher parent anxiety, and higher parent pain catastrophizing were associated with increased disability in children at 3 months post injury

Fisher, Emmaa,*; Monsell, Fergalb; Clinch, Jacquib,c; Eccleston, Christophera,d. Who develops chronic pain after an acute lower limb injury? A longitudinal study of children and adolescents. PAIN 165(11):p 2507-2516, November 2024. | DOI: 10.1097/j.pain.0000000000003274 

Job Stress and Chronic Low Back Pain: incidence, number of episodes, and severity in a 4 year follow up of the ELSA-Brasil Musculoskeletal Cohort

• Work conditions play a significant role in the occurrence of low back pain
• Physical, ergonomic, and stress factors are associated with low back pain
• The “effort-reward imbalance” model suggests that high work effort combined with insufficient rewards leads to stress which leads to musculoskeletal symptoms
• This study showed that high job stress increases the likelihood of developing chronic low back pain. Low rewards also increases the risk.

Hubner, Fernanda Corsino Limaa; Telles, Rosa Weissb; Giatti, Luanaa,b; Machado, Luciana A. C.b,c; Griep, Rosane Harterd; Viana, Maria Carmene; Barreto, Sandhi Mariaa,b; Camelo, Lidyane V.a,b,*. Job stress and chronic low back pain: incidence, number of episodes, and severity in a 4-year follow-up of the ELSA-Brasil Musculoskeletal cohort. PAIN 165(11):p 2554-2562, November 2024. | DOI: 10.1097/j.pain.0000000000003276 

Mepivacaine instillation for pain reduction during intrauterine device placement in nulliparous women: a double-blind randomized trial

• It is common for women to have a fear of pain with IUD insertion
• This study included 151 women with 76 in the mepivacaine group and 75 in the placebo group. 93.3% of the women in the mepivacaine group reported tolerable pain during placement whereas 80.3% of participants in the placebo group reported tolerable pain.

Mepivacaine instillation for pain reduction during intrauterine device placement in nulliparous women: a double-blinded randomized trial
Envall, Niklas et al.
American Journal of Obstetrics & Gynecology, Volume 231, Issue 5, 524.e1 – 524.e7

Nociplastic Pain Mechanisms and toll-like receptors as promising targets for its management

• Chronic pain is often neuropathic or nociplastic
• Nociplastic pain includes fibromyalgia, temporomandibular joint disorder, and chronic pelvic pain
  • Associated with fatigue, sleep disturbances, and cognitive dysfunction
  • Influenced by altered central nervous system processing, neuroinflammation, and immune dysregulation
• Toll-like receptors (TLR) are a part of the immune system and amplify pain signals through neuroinflammation
  • Activated by stress and sleep deprivation
  • Potential therapeutic targets to reduce nociplastic pain by dampening neuroinflammation
• TLRs are believed to play a big role in the development of fibromyalgia
  • Highly active in immune cells that release proinflammatory immune receptors
  • Macrophages and monocytes infiltrate areas near nerve fibers
  • Pt w/ fibromyalgia show elevated levels of IL-1B, IL-6, and TNF-a
  • Blocking TLR signaling reduces pain sensitivity in fibromyalgia models by lowering cytokine levels
• TLRs are involved in modulating ion channels linked to pain sensitivity
• Prolonged stress can lead to neuroendocrine changes, neuroinflammation, depression, and anxiety
  • Stress induced pain is linked to increased noradrenaline levels
  • Blocking adrenaline production can reduce pain hypersensitivity
  • Prolonged stress→ release of proinflammatory cytokines, sensitizing pain receptors
  • There are increased levels of TLRs in the spinal cord and dorsal root ganglia in response to stress
• Complex regional pain syndrome has been associated with elevated adrenergic receptors
  • Pain is sustained by the sympathetic nervous system

Rodríguez-Palma, Erick J.a,b; Huerta de la Cruz, Saulc; Islas-Espinoza, Ana M.b; Castañeda-Corral, Gabrielad; Granados-Soto, Viniciob; Khanna, Rajesha,*. Nociplastic pain mechanisms and toll-like receptors as promising targets for its management. PAIN 165(10):p 2150-2164, October 2024. | DOI: 10.1097/j.pain.0000000000003238 

Barriers and enablers to exercise adherence in people with nonspecific chronic low back pain: a systematic review of qualitative evidence

• Adherence to exercise is an important aspect to managing chronic low back pain for long term benefits
  • A single exercise session is usually not enough to reduce pain; consistency is key
  • Up to 70% of people w/ chronic low back pain fail to adhere to prescribed home exercises
• Research has identified over 200 factors associated with exercise adherence

Gilanyi, Yannick L.a,b,*; Shah, Brishnaa,b; Cashin, Aidan G.a,b; Gibbs, Mitchell T.a,b; Bellamy, Jessicaa; Day, Richardc; McAuley, James H.a,b; Jones, Matthew D.a,b. Barriers and enablers to exercise adherence in people with nonspecific chronic low back pain: a systematic review of qualitative evidence. PAIN 165(10):p 2200-2214, October 2024. | DOI: 10.1097/j.pain.0000000000003234 

The prevalence of chronic pain in children and adolescents: a systematic review update and meta-analyses

• Chronic pain in children and adolescents can lead to functional impairment, social isolation, mental health issues, and long-term consequences that extend into adulthood
• Higher prevalence in girls
  • Higher rates of headaches and multisite pain
• 20.8% of children globally experience chronic pain

Chambers, Christine T.a,b,c,*; Dol, Justinea; Tutelman, Perri R.a,b; Langley, Charlotte L.a; Parker, Jennifer A.a; Cormier, Brittany T.a; Macfarlane, Gary J.d; Jones, Gareth T.d; Chapman, Darlenee; Proudfoot, Nicolea; Grant, Amyf; Marianayagam, Justinag. The prevalence of chronic pain in children and adolescents: a systematic review update and meta-analysis. PAIN 165(10):p 2215-2234, October 2024. | DOI: 10.1097/j.pain.0000000000003267 

Eliciting the rubber hand illusion by the activation of nociceptive c and a fibers

• There is this concept of body ownership. You know that your hand is your hand and your foot is your foot.
• Then there is the rubber hand illusion (RHI). This involves stroking the participants real hand (which they can’t see) and simultaneously stroking a rubber hand (which they can see). This induces the illusion that the rubber hand is part of the participant’s body. 

Pain reflects the informational value of nociceptive inputs

• Pain signals danger and teaches us to avoid future threats
• Prior expectations can influence pain transmission from the spinal cord to the brain

Coll, Michel-Pierrea,b; Walden, Zoeyc; Bourgoin, Pierre-Alexandred; Taylor, Veroniquee; Rainville, Pierref,g; Robert, Manonh; Nguyen, Dang Khoah; Jolicoeur, Pierrei; Roy, Mathieuc,j,*. Pain reflects the informational value of nociceptive inputs. PAIN 165(10):p e115-e125, October 2024. | DOI: 10.1097/j.pain.0000000000003254 

The downside to choice: instrumental control increases conditioned nocebo hyperalgesia

• Nocebo hyperalgesia: the expectation of pain heightens the pain experience without pharmacological causes
  • Driven by verbal, social, and conditioned cues
• Having control over aversive experiences, such as choosing coping strategies, can increase pain tolerance
• This study found that offering choice increased nocebo hyperalgesia

The relationship between traumatic exposure and pain perception in children: the moderating role of posttraumatic symptoms

• This study investigated the relationship between adverse childhood experiences and pain sensitivity in children 
• Adverse childhood experiences (ACEs) are traumatic events before the age of 18
  • More than half of children globally have experienced one ACE
  • Closely linked with chronic pain and altered pain perception in adulthood
• Aults w/ history of ACEs tend to have lower pain thresholds and greater pain sensitivity

Levy Gigi, Einata,b,*; Rachmani, Moriyaa; Defrin, Ruthc. The relationship between traumatic exposure and pain perception in children: the moderating role of posttraumatic symptoms. PAIN 165(10):p 2274-2281, October 2024. | DOI: 10.1097/j.pain.0000000000003266 

Risk of adverse outcomes during gabapentinoid therapy and factors associated with increased risk in UK primary care using the clinical practice research datalink: a cohort study

• Gabapentinoids include gabapentin and pregabalin. They are anticonvulsants that have been approved for the treatment of epilepsy, neuropathic pain, and generalized anxiety disorder.
• Prescriptions for these drugs have significantly increased over the last two decades.
• 60% of patients experience central nervous system side effects: drowsiness, dizziness, ataxia
  • Increased risk of falls and injuries in older adults
• There are now higher rates of gabapentinoid abuse, especially w/ pregabalin due to its rapid absorption and faster action
  • Usually occurs in individuals with a history of substance abuse
  • Pregabalin is associated with higher rates of overdose

Muller, Saraa,*; Bailey, Jamesa; Bajpai, Rama; Helliwell, Tobya,b; Harrisson, Sarah A.a,b; Whittle, Rebeccaa,c; Mallen, Christian D.a; Ashworth, Juliea,b. Risk of adverse outcomes during gabapentinoid therapy and factors associated with increased risk in UK primary care using the clinical practice research datalink: a cohort study. PAIN 165(10):p 2282-2290, October 2024. | DOI: 10.1097/j.pain.0000000000003239 

Parental narrative style moderates the relation between pain-related attention and memory biases in youth with chronic pain

• Negatively biased pain memories: individuals recall higher levels of pain and fear than initially reported
  • Risk factor for increased pain and distress during future painful experiences
• Biased memories are influential in predicting children’s future pain, anxiety, and distress
• Parental narrative style impacts the way their children experience pain
  • Parents who use more elaborative and emotionally rich conversations mitigate the effects of pain attention bias

Wauters, Alinea,*; Van Ryckeghem, Dimitri M.L.a,b,c; Noel, Melanied; Mueri, Kendrad; Soltani, Sabined; Vervoort, Tinea. Parental narrative style moderates the relation between pain-related attention and memory biases in youth with chronic pain. PAIN 165(10):p e126-e137, October 2024. | DOI: 10.1097/j.pain.0000000000003263 

High impact chronic pain in sickle cell disease: insights from the pain in sickle cell epidemiology study

• Chronic pain is common in those with SCD. Over half of people w/ SCD report chronic pain and one-third report nearly daily pain.
• Some individuals have high impact chronic pain

Jagtiani, Ashnaa,b; Chou, Erica,b; Gillespie, Scott E.c; Liu, Katiec; Krishnamurti, Lakshmanand; McClish, Donnae; Smith, Wally R.f; Bakshi, Nityaa,b,*. High-impact chronic pain in sickle cell disease: insights from the Pain in Sickle Cell Epidemiology Study (PiSCES). PAIN 165(10):p 2364-2369, October 2024. | DOI: 10.1097/j.pain.0000000000003262 

Low Dose Naltrexone’s utility for non-cancer centralized pain conditions: a scoping review

• Naltrexone is typically used in high doses (50-100 mg) to treat opioid and alcohol dependence
• At lower doses (4.5 mg) it is referred to as low dose naltrexone and it binds to toll-like receptor 4 on microglial cells in the central nervous system
  • This reduces neuroinflammation
  • Low dose naltrexone can be beneficial for people with fibromyalgia, complex regional pain syndrome, and irritable bowel syndrome
  • Associated w/ improvements in function, sleep, mood, and quality of life
  • Doses range from 1 to 9 mg
• There is some evidence suggesting that low dose naltrexone may enhance the efficacy of opioids

Rupp A, Young E, Chadwick AL. Low-dose naltrexone’s utility for non-cancer centralized pain conditions: a scoping review. Pain Med. 2023 Nov 2;24(11):1270-1281. doi: 10.1093/pm/pnad074. PMID: 37302106; PMCID: PMC10628981.