Acute Pain Effects on Motor Skills

Overseen By Ashley Fath

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Delaware

Must not be taking: Analgesics

Disqualifiers: Mental health, Cardiovascular, Neurological, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 1 day

68 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how short-term pain affects the learning and memory of movement skills, particularly in older adults. Researchers aim to determine if pain hinders the ability to learn and remember new movements and whether this effect is more pronounced in older individuals due to normal aging. Participants will either receive a mild pain stimulus using capsaicin and heat on the skin or no stimulus at all. Those who are generally healthy, willing to experience mild pain or non-painful sensations, and have no significant medical or mental health conditions might be suitable candidates. As an unphased trial, this study allows participants to contribute to understanding the impact of pain on movement learning and memory.

Do I need to stop taking my current medications for the trial?

Yes, you will need to stop taking any analgesic medications or treatments for pain relief, except for baby aspirin used for heart health.

What prior data suggests that this protocol is safe for older adults?

Research has shown that using capsaicin with heat, as in this trial, is generally safe for people. Studies have found that applying capsaicin to the skin is usually well-tolerated, though it can cause mild side effects. These may include temporary pain upon application, redness, or reduced sensitivity to heat. Capsaicin often eases pain from nerve problems, supporting its safety.

Capsaicin is a strong irritant and can cause a burning sensation on the skin. This reaction is normal and expected. Overall, previous studies suggest that while some discomfort may occur, the treatment is relatively safe for people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how acute pain affects motor skills, which is a relatively uncharted area. Unlike standard pain management options like analgesics or physical therapy, this trial uses a unique method of applying capsaicin combined with heat to the skin to induce a pain stimulus. This approach allows scientists to observe the immediate effects of pain on motor function, shedding light on how pain might disrupt physical performance. By understanding these effects, the trial could lead to new insights that improve pain management strategies and rehabilitation programs.

What evidence suggests that this trial's treatments could be effective for acute pain effects on motor skills?

This trial will compare the effects of a pain stimulus with no stimulus on motor skills. Research has shown that sudden pain can influence the learning of physical movements, though the effects vary. Some studies found that pain from spicy substances or heat could hinder the retention of motor skills. However, other research suggests that such pain might actually aid in learning new movements. The location of the pain appears to have little impact, and spicy substances might even serve as a distraction that aids learning. Overall, the impact of pain on learning motor skills is complex and situation-dependent. ^{3 6 7 8 9}

Who Is on the Research Team?

Susanne M Morton, PhD

Principal Investigator

University of Delaware

Are You a Good Fit for This Trial?

This trial is for medically healthy young adults aged 18-35 and older adults aged 55-85 who can read, write, and speak English. They must be able to consent and attend all sessions, willing to experience experimental pain or non-painful stimulation. Young participants will be sex-matched with an older participant.

Inclusion Criteria

My sex matches someone in the older adult group.

Self-identifying as generally medically healthy

Able to provide informed consent and attend all testing sessions

Exclusion Criteria

I have had balance issues, felt dizzy, or fallen more than once in the past year.

I have numbness or weakness in my legs or the area to be treated.

Score on the GAD-7 ≥ 10

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either a pain stimulus or no stimulus to study the effects on motor learning

1 day

1 visit (in-person)

Follow-up

Participants are monitored for retention of locomotor learning and cognitive performance

24 hours

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• distractor delivery
• pain delivery

Trial Overview The study investigates how acute pain affects learning new motor skills like walking in both young and older adults. It looks at whether pain changes how well they remember these skills later on, especially if cognitive decline due to aging plays a role.

How Is the Trial Designed?

Group I: Pain Stimulus Experimental Treatment 1 Intervention

Capsaicin combined with heat applied to intact skin

Group II: No Stimulus Active Control 1 Intervention

Nothing applied to skin

Who Is Running the Clinical Trial?

University of Delaware

Lead Sponsor

Trials

167

Recruited

25,700+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

The new fast-dissolving acetaminophen tablet formulation (FD-APAP) disintegrates significantly faster than standard acetaminophen tablets, with a mean disintegration time of 12.9 minutes compared to 69.6 minutes (P < 0.0001).

FD-APAP also shows a quicker absorption rate, with a median time to peak concentration (Tmax) of 0.50 hours versus 0.67 hours for standard acetaminophen (P < 0.01), potentially leading to improved pain relief outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of a novel fast-dissolving acetaminophen tablet formulation (FD-APAP) and standard acetaminophen tablets using gamma scintigraphy and pharmacokinetic studies. Wilson, CG., Clarke, CP., Starkey, YY., et al.[2022]

A fast-dissolving formulation of paracetamol (FD-APAP) at 1000 mg provided significantly greater pain relief and faster onset compared to both a lower dose of FD-APAP (500 mg) and standard paracetamol (650 mg) in patients after dental surgery, with the first perceptible relief occurring in just 15 minutes.

All treatments were well tolerated, indicating that FD-APAP 1000 mg is a safe and effective option for managing acute pain, particularly in postsurgical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and speed of onset of pain relief of fast-dissolving paracetamol on postsurgical dental pain: two randomized, single-dose, double-blind, placebo-controlled clinical studies. Yue, Y., Collaku, A., Brown, J., et al.[2013]

Paracetamol (acetaminophen) is commonly used for pain relief and fever reduction during pregnancy, but recent studies suggest that prenatal exposure may negatively impact fetal development, potentially leading to neurodevelopmental and reproductive disorders.

Given these concerns, experts recommend that pregnant women should avoid using paracetamol unless medically necessary, consult healthcare professionals for guidance, and use the lowest effective dose for the shortest duration if it is deemed necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paracetamol use during pregnancy - a call for precautionary action. Bauer, AZ., Swan, SH., Kriebel, D., et al.[2022]

In a study involving 40 healthy volunteers, acetaminophen (APAP) was found to improve cognitive performance, specifically in decision-making and spatial planning tasks, while also providing pain relief without affecting body temperature.

The results suggest that the cognitive benefits of APAP are linked to its analgesic effects rather than its impact on thermoregulation, indicating a potential connection with serotonergic and cannabinoid systems that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paracetamol sharpens reflection and spatial memory: a double-blind randomized controlled study in healthy volunteers. Pickering, G., Macian, N., Dubray, C., et al.[2018]

In a randomized study involving 603 adults with ankle sprains, both tramadol/acetaminophen and hydrocodone/acetaminophen provided significantly greater pain relief compared to placebo within the first 4 hours after administration.

The study found no significant difference in efficacy between tramadol/acetaminophen and hydrocodone/acetaminophen, indicating that both medications are equally effective and well-tolerated for treating acute musculoskeletal pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tramadol/acetaminophen or hydrocodone/acetaminophen for the treatment of ankle sprain: a randomized, placebo-controlled trial. Hewitt, DJ., Todd, KH., Xiang, J., et al.[2013]

Chronic use of paracetamol (acetaminophen) has been linked to significant adverse effects, including an increased risk of gastrointestinal bleeding and a small rise in systolic blood pressure (~4 mmHg), which are dose-dependent.

The evidence regarding the long-term safety of paracetamol is primarily based on cohort and observational studies, with few randomized controlled trials, highlighting the need for careful consideration and discussion of potential side effects when prescribing it for chronic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term adverse effects of paracetamol - a review. McCrae, JC., Morrison, EE., MacIntyre, IM., et al.[2023]

Paracetamol (acetaminophen) is an effective first-line treatment for moderate pain, showing significant analgesic effects in various acute pain situations, including perioperative settings and conditions like migraines and musculoskeletal pain.

It has a favorable safety profile, with no clinically relevant adverse effects at recommended doses, and can enhance pain relief when used alongside other medications, such as opioids and non-steroidal anti-inflammatory drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of paracetamol in the acute pain management]. Kehlet, H., Werner, MU.[2019]

In a study involving 97 children aged 6 to 12 with pharyngotonsillitis, paracetamol syrup was found to be significantly more effective than placebo in reducing pain, as reported by both children and parents.

Both paracetamol and ketoprofen lysine salt were shown to be safe and effective analgesics for treating sore throat in children, with no significant adverse effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled trial of paracetamol and ketoprofren lysine salt for pain control in children with pharyngotonsillitis cared by family pediatricians. Ruperto, N., Carozzino, L., Jamone, R., et al.[2021]

Paracetamol (acetaminophen) is one of the most widely used pain relievers and fever reducers globally, with a long history of use as an analgesic-antipyretic drug.

Recent research has provided important insights into its toxicity, pharmacokinetics, and mechanisms of action, enhancing our understanding of its therapeutic efficacy over the past decade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Paracetamol. Present status of knowledge in 1989]. Lechat, P., Kisch, R.[2013]

A systematic review of 12 clinical trials and 1 observational study on paracetamol for inflammatory arthritis found weak evidence supporting its effectiveness over placebo, particularly in patients with rheumatoid arthritis.

While paracetamol may provide some additive benefit when used with NSAIDs, its safety profile remains uncertain, with one study suggesting a higher risk of serious gastrointestinal events when used alongside corticosteroids and other analgesics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paracetamol for the management of pain in inflammatory arthritis: a systematic literature review. Hazlewood, G., van der Heijde, DM., Bombardier, C.[2018]

In a study of 119 patients undergoing breast surgery or thyroidectomy, propacetamol provided effective postoperative pain relief, with over 90% of patients not requiring additional analgesics.

While both systematic and demand-based administration of propacetamol showed similar pain relief, the systematic group received higher doses and experienced fewer instances of pain during infusion, indicating that systematic administration may be more beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of propacetamol in postoperative pain based on two modes of intravenous administration]. Farhat, F., Savoyen, MC., Jayr, C.[2013]

Ibuprofen has been shown to be effective for treating acute migraine attacks in children, providing pain relief at 2 hours compared to a placebo, with no significant difference in adverse events reported.

Paracetamol did not demonstrate a significant difference in efficacy compared to placebo, and there was no notable difference in effectiveness between ibuprofen and paracetamol for treating migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of acute migraine attacks in children with analgesics on the World Health Organization Essential Medicines List: A systematic review and GRADE evidence synthesis. Jeric, M., Surjan, N., Jelicic Kadic, A., et al.[2019]

In a study of 120 children undergoing cleft palate surgery, the combination of rectal acetaminophen and diclofenac provided the best pain relief compared to either medication alone or placebo, especially in the first 12 hours post-surgery.

Both acetaminophen and diclofenac were more effective than placebo, with diclofenac showing superior pain control compared to acetaminophen, while adverse effects were similar across all treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of rectal diclofenac and acetaminophen alone and in combination on postoperative pain after cleft palate repair in children. Mireskandari, SM., Makarem, J.[2013]

Prenatal exposure to paracetamol is associated with a 30% increased risk of overall cerebral palsy (CP) and a 50% increased risk of unilateral spastic CP, particularly when taken during the second trimester, based on a study of 185,617 mother-child pairs.

Aspirin use during pregnancy is linked to a 140% increased risk of bilateral spastic CP, suggesting that both paracetamol and aspirin may adversely affect neurodevelopment in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of paracetamol, ibuprofen or aspirin in pregnancy and risk of cerebral palsy in the child. Petersen, TG., Liew, Z., Andersen, AN., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12416618/

Acute Pain Impairs Retention of Locomotor Learning ... Our group and others have shown that the presence of an acute painful stimulus may interfere with retention of motor learning.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5102313/

Interactive effect of acute pain and motor learning acquisition ... Enhanced learning was found when motor skill acquisition took place in the presence of acute capsaicin-induced experimental pain, indicating that pain does ...

3. researchgate.net researchgate.net/publication/349289870_Assessment_of_motor_skill_accuracy_and_coordination_variability_after_application_of_local_and_remote_experimental_pain

(PDF) Assessment of motor skill accuracy and coordination ... The results revealed that pain had no impact on dart-throwing skill acquisition, and there was no significant difference (p = 0.732) among the ...

4. mdpi.com mdpi.com/2076-3425/8/10/179

Does Location of Tonic Pain Differentially Impact Motor ... The fact that motor learning improved regardless of the location of acute tonic pain suggests that capsaicin may have a potential role as a distractor from the ...

5. researchgate.net researchgate.net/publication/223547193_Transient_inhibition_of_the_human_motor_cortex_by_capsaicin-induced_pain_A_study_with_transcranial_magnetic_stimulation

Transient inhibition of the human motor cortex by capsaicin ... ... It is noted that the thermode was applied 20 minutes after capsaicin treatment, and pain sensations only reached 2 to 3 by this time. 26, ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0163725820302746

Neurobiology of capsaicin-induced analgesia for chronic ... The safety of topical capsaicin is well validated, and adverse side effects, such as procedural pain, erythema, or reduced heat sensitivity, are considered ...

7. en.wikipedia.org en.wikipedia.org/wiki/Capsaicin

Capsaicin It is a potent irritant for mammals, including humans, for which it produces a sensation of burning in any tissue with which it comes into contact. Capsaicin ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/capsaicin-topical-route/description/drg-20062561

Capsaicin (topical route) - Side effects & dosage Capsaicin is used to help relieve a certain type of pain known as neuralgia (shooting or burning pain in the nerves).

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11305642/

Acute pain impairs retention of locomotor learning - PMC Acute pain, such as the experimental pain we induced with capsaicin and heat, has been shown to reduce corticomotor excitability in M1 (12, 19–21, 50, 51).