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

Trial Summary

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 data supports the effectiveness of the drug Paracetamol for acute pain effects on motor skills?

Research shows that Paracetamol (also known as acetaminophen) is effective in reducing pain after surgeries, such as cleft palate repair in children, and is widely used for its pain-relieving properties. This suggests it may help manage acute pain, which could indirectly support motor skills by reducing discomfort. ^{1 2 3 4 5}

Is paracetamol generally safe for humans?

Paracetamol (also known as acetaminophen) is widely used and generally considered safe for short-term use in humans when taken as directed. However, long-term use may increase the risk of gastrointestinal bleeding and slightly raise blood pressure. Pregnant women should use it cautiously, as it might affect fetal development. ^{6 7 8 9 10}

How does this drug differ from other treatments for acute pain?

This treatment uses acetaminophen, which is unique for its ability to relieve pain without the significant side effects often associated with stronger pain medications like opioids. It is also part of a 'multimodal analgesia' approach, meaning it can be combined with other pain relievers to enhance effectiveness while minimizing the need for higher doses of any single drug. ^{5 11 12 13 14}

What is the purpose of this trial?

To date, the effects of pain on motor learning have not been thoroughly investigated, particularly in older adults. Broadly, the purpose of this research is to investigate the impact of acute pain on locomotor learning and its retention in older adults. The investigators hypothesize that acute pain impairs retention of locomotor learning in young and older adults and that in older adults, these deficits are worsened and are related to the degree of normal age-related cognitive decline.

Research Team

Susanne M Morton, PhD

Principal Investigator

University of Delaware

Eligibility Criteria

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

I am willing to undergo experimental electrical stimulation.

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. England 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. [2021]

3. France pubmed.ncbi.nlm.nih.gov

[Paracetamol. Present status of knowledge in 1989]. [2013]

4. France pubmed.ncbi.nlm.nih.gov

[Efficacy of propacetamol in postoperative pain based on two modes of intravenous administration]. [2013]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Paracetamol sharpens reflection and spatial memory: a double-blind randomized controlled study in healthy volunteers. [2018]

6. Canada pubmed.ncbi.nlm.nih.gov

Paracetamol for the management of pain in inflammatory arthritis: a systematic literature review. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Paracetamol use during pregnancy - a call for precautionary action. [2022]

8. England 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. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Use of paracetamol, ibuprofen or aspirin in pregnancy and risk of cerebral palsy in the child. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Long-term adverse effects of paracetamol - a review. [2023]

11. New Zealand pubmed.ncbi.nlm.nih.gov

[Role of paracetamol in the acute pain management]. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Tramadol/acetaminophen or hydrocodone/acetaminophen for the treatment of ankle sprain: a randomized, placebo-controlled trial. [2013]

13. England 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. [2022]

14. United States 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. [2013]