- Infographic: partner EFIC has created an infographic to help you quickly grasp what IMI-PainCare is all about.
- Handout IMI-PainCare: This pdf is a brochure with more detailed information about the project
- IMI-PainCare flyer: This pdf encodes a flyer with some overview information about the project
- A pdf with information on pelvic pain published in the New Scientist
- Many of our reports are available via the Cordis project page here.
Summaries of publications for the general public
Pogatzki-Zahn, Esther et al.
Pogatzki-Zahn, Esther M et al. “Developing consensus on core outcome domains for assessing effectiveness in perioperative pain management: results of the PROMPT/IMI-PainCare Delphi Meeting” Pain vol. 162,11 (2021): 2717-2736. https://doi.org/10.1097/j.pain.0000000000002254
Many patients experience severe pain after surgery, and sometimes this pain even becomes chronic. If pain is not treated well immediately after surgery, patients suffer, their recovery from the operation can be impaired and they often need strong painkillers, like for example opioids. This is what makes pain management after surgery so important.
To implement better pain treatments, we need to improve our understanding of what makes a treatment successful. Currently, how we measure the success of treatments for pain varies significantly. Is a treatment considered successful if it changes the intensity of pain, pain interference, has low harms, or anything else? Until there is agreement on the most important things to measure, it is very difficult to say if a pain treatment is successful.
The aim of this study was to identify the treatment goals of pain management after surgery and to find out how to best assess these goals. An invited panel of international health-care representatives and experts in their field (like surgeons, anaesthesiologists, pain specialists, nurses, physiotherapists, psychologists etc) as well as patient representatives discussed these questions. . All members of the panel met face-to-face and were engaged in group discussions and brainstorming. Important was that the visions of all participants were expressed, discussed and taken into consideration. At the end, all participants voted on a final list of those aspects (“domains”) important for assessing the success of treatments for pain after surgery.
The panel voted on the final list of domains to be measured. The panel decided that five aspects should be addressed: 1. Physical function/ability, 2. Level of pain at rest, 3. Level of pain during activity, 4. Harms of treatment, and 5. Patient confidence (“self-efficacy”) in managing their pain after surgery. The last, and somehow unexpected aspect, was brought up by nurses and patients and points to a new direction in acute pain assessment. The next step will be to identify the best suited measures relevant for assessing these pain-related domains after surgery.
Sachau, Juliane et al.
Sachau, Juliane et al. “Patient Reported Outcome Measures in Chronic Neuropathic Pain Clinical Trials - A Systematic Literature Review” The Journal of Pain vol. 24,1 (2023): 38-54. https://doi.org/10.1016/j.jpain.2022.09.003
For a nerve pain drug to be considered helpful, it needs to have an effect on domains seen as important by the patient living with the pain condition. These are called patient reported outcome measures. One is pain severity. Others include physical functioning (e.g. movement), emotional functioning (e.g. mood), side effects of the treatment, and patient satisfaction. These various domains should be measured in all clinical trials – where scientists are investigating the effect of a drug on a patient with nerve pain. We reviewed all nerve pain clinical trials which examined the effect of a drug on long term nerve pain to see what domains they measure, and how they compare across trials. While there has been an improvement in the number of high-quality trials measuring a range of these measures since 2011, there is still large variation between trials, and major room for improvement. Ensuring future clinical trials consistently measure a range of patient reported measures is crucial to better understanding the effect of drugs on patients living with nerve pain.
Gierthmühlen, Janne et al.
Gierthmühlen, Janne et al. “Association of sensory phenotype with quality of life, functionality, and emotional well-being in patients suffering from neuropathic pain” Pain vol. 163,7 (2022): 1378-1387. https://doi.org/10.1097/j.pain.0000000000002501
Patients with neuropathic pain - pain, numbness, tingling, swelling, or muscle weakness caused due to nerve injury or disorder – present in a different ways with a range of characteristics. Patients often present in 3 different ways:
- Sense loss (e.g. numbness, muscle weakness),
- Increased sensitivity to physical things (e.g exaggerated pain in response to movement or pin-prick), or
- Increased sensitivity to temperature (e.g. exaggerated pain in response to heat and/or cold).
These three characteristics may indicate different underlying causes, that may benefit from individualised treatments. In this study of 433 patients with various neuropathic pain conditions, we examined differences in mental health, physical function, and quality of life between patients with one of the three pain characteristics mentioned above. The study found no differences in disability, pain intensity, depression, anxiety between patients categorized into one of the three pain characteristics. Patients with the sense loss had higher pain interference, lower quality of life, and more problems with movement, activities of daily living and self-care compared to patients with increased sensitivity to temperature. Patients with sense loss had a higher tendency to ruminate and think negatively about their pain condition compared to patients with increased sensitivity to physical things and temperature.
In summary, certain pain characteristics – in this case sensory loss (e.g numbness) – have a large effect on patient suffering compared to other neuropathic pain presentations. Patients with sensory loss may benefit from more individualised tailored treatment to help their condition.
Harkouk, Hakim et al.
Harkouk, Hakim et al. “Paravertebral block for the prevention of chronic postsurgical pain after breast cancer surgery” Regional anesthesia and pain medicine vol. 46,3 (2021): 251-257. https://doi.org/10.1136/rapm-2020-102040
Patients who undergo breast cancer surgery often report long lasting pain after their surgery. A paravertebral block (an injection of pain medicine in between the spinal bones where the spinal nerve come out) may prevent this pain, but we are uncertain about the evidence. In this study, we compiled and reviewed all the available trials that have examined the effect of a paravertebral block on preventing long lasting pain after breast cancer surgery. This is important to do as it informs us if this treatment is helpful or not. Twelve trials were compiled, and their methods and results were reviewed. Based on these trials, a paravertebral injection does not seem to prevent long term pain after breast cancer surgery. Larger and higher quality studies are required to reach more definitive conclusions.
Quesada, Charles et al.
Quesada, Charles et al. “Human surrogate models of central sensitization: A critical review and practical guide” European journal of pain (London, England) vol. 25,7 (2021): 1389-1428. https://doi.org/10.1002/ejp.1768
Current medicines for chronic pain are not very effective. Neuropathic pain – pain relating to diseases of the warning system of the body (“nociceptive system”)– is particularly difficult to manage. Neuropathic pain often involves increased sensitivity to stimulation of the skin: increased pain to stimuli that should be just barely painful (hyperalgesia) and pain in response to stimuli that are normally not painful (allodynia). Animal experiments have shown that this increased sensitivity is often due to signal amplification in the central nervous system (spinal cord and brain) that is called “central sensitization”. But findings from animal experiments are difficult to translate to humans. Mimicking increased sensitivity of the central nervous system (hyperalgesia and allodynia) in humans, through experiments on healthy volunteers, may aid our understanding of this pain and help to identify new targets for medicines.
The aim of this study was to gather and review all currently available research studies that have attempted to induce increased sensitivity of the central nervous system in humans, through a real or simulated tissue injury. Success rate, accuracy, feasibility of the methods used, as well as drug response, were analysed.
Analysis of 269 studies involving 15 different methods of inducing central sensitization revealed that four methods were reliable in inducing hyperalgesia: application or injection of capsaicin (chemical compound from chilli peppers), heat injury, repetitive electrical stimulation, and ultraviolet B rays (sunburn). As a limitation, these methods were poor at inducing allodynia. The capsaicin, heat injury and electrical stimulation models consistently responded to medicines that are effective for neuropathic pain management and not to medicines that are clinically ineffective. Thus, these models reflect some aspects of neuropathic pain in healthy volunteers; the methods used are easy to use in the clinic and may inform the development of better treatments for chronic pain.
Di Lionardo, A et al.
Di Lionardo, A et al. “Modulation of the N13 component of the somatosensory evoked potentials in an experimental model of central sensitization in humans” Scientific reports vol. 11,1 20838. 21 Oct. 2021, https://doi.org/10.1038/s41598-021-00313-7
Increased pain sensitivity (hyperalgesia) occurs for a short period of time at and around minor and major acute injuries (e.g. cuts, burns). It is also an important feature of many chronic pain conditions. After a tissue injury, various chemicals in the body (e.g. ones responsible for inflammation) produce increased sensitivity in neurons around the area of the injury. This is seen as an important survival mechanism as it can help prevent us from doing more injury. This protective response produces an increase in the amount of inputs (e.g. messages about threat/danger) sent to the spinal cord. This increase in inputs can lead to the production of increased sensitivity in uninjured areas, which if maintained can contribute to long term pain states - long after the initial injury has healed. This happens in central nervous system sensitization which is defined as an increase in the excitability or responsiveness of neurons. How to reliably identify and measure central sensitization in patients is still an matter of uncertainty, and is critical to research for scientists to better target this state in patients.We studied a small electrical signal that is believed to be generated by nerve cells in the spinal cord; many stimulus repetitions need to be recorded and averaged to visualize this signal that is called “N13” (negativity 13 ms after electrical stimulation of the ulnar nerve). The N13 component of somatosensory evoked potentials (N13 SEP) is recorded in front–back direction from the lower neck (Cv6) after upper limb stimulation is mediated by non-nociceptive Aβ fibres. This component , generated at the cervical dorsal horn, probably reflects the segmental postsynaptic response of dorsal horn neurons in the lower cervical grey matter, and might therefore constitute a neurophysiological measure sensitive to the excitability changes of dorsal horn neurons during central sensitization.
Different experimental pain models have been devised to produce central sensitization in humans, among them topical application of capsaicin that leads to intensive activation of C and Aδ nociceptive nerve fibres, producing burning pain.
In this neurophysiological study in healthy humans, it has been investigated if and how capsaicin-induced central sensitization modulates the dorsal horn N13 SEPs and whether pregabalin, a first-line treatment for neuropathic pain targeting voltage-gated calcium channels expressed in the dorsal horn and the brain, is able to modulate capsaicin-induced N13 SEP sensitization. The study demonstrated in healthy participants that central sensitization induced by topical capsaicin was associated with an increase in the amplitude of the dorsal horn N13 SEP. Furthermore, it showed that pregabalin, a drug with proven efficacy on dorsal horn neurons, prevented the N13 SEP modulation associated with capsaicin-induced central sensitization. These findings suggest that N13 SEP reflects changes in dorsal horn excitability and might represent a biomarker of central sensitization in humans.
Endometriosis and interstitial cystitis/bladder pain syndrome are both associated with debilitating chronic pelvic pain. Effective treatments for the pain are limited. Findings from animal models of disease have been used for the development of treatments for the chronic pelvic pain associated with endometriosis and IC/BPS, however these findings have failed to develop new, effective treatments for patients. It is vital that animal experiments are high quality and representative to translate effectively to humans.
The aim of this study was to review currently available models of endometriosis and bladder pain syndrome in rodents to examine how well they replicate the pain experience of patients. 1009 papers focussed on endometriosis. 41% used a model where tissue from the womb of each rodent was placed into a different part of its pelvis (known as autologous transplantation). 26% used a model where tissue from the womb of a mouse was placed into a different mouse (known as syngeneic transplantation). 18% used a model where human tissue from endometriosis lesions themselves were placed in mice who had also had their immune systems suppressed (known as xenograft transplantation). 11% used a model where tissue from the womb of mouse was placed into a different mouse but of the same species (known as allogenic transplantation). It was concluded that the syngeneic model was the most valid for resembling lesion characteristics in rodents.
1055 papers focussed on bladder pain syndrome. 85% of models were focussed on bladder alterations. 8% were complex mechanism models and stress-induced models, respectively. Across these models, the most frequently used were those placing irritants in the bladder (92%), those altering the immune system (43%), and a model that induces stress by water avoidance (39%), respectively.
A minority of both endometriosis (<12%) and bladder pain syndrome studies (<44%) examined measures associated with pain. Further, only 2% and 3% of papers used endometriosis and bladder pain syndrome models investigating spontaneous pain measures.
Overall, the study demonstrates that pain rarely features in published papers which aim to create an effective rodent model for developing effective treatments for the chronic pelvic pain associated with endometriosis and bladder pain syndrome. Researchers need to develop better animal models, share their experimental protocols, and include spontaneous pain readouts to evaluate chronic pelvic pain in their experiments.
The Unmet Needs for Studying Chronic Pelvic/Visceral Pain Using Animal Models
Neto AC, et al.; Biomedicines 2023, 11(3), 696
Rodent Animal Models of Endometriosis-Associated Pain: Unmet Needs and Resources Available for Improving Translational Research in Endometriosis
Tejada, MA et al. International journal of molecular sciences vol. 24,3 2422. 26 Jan. 2023
Patient Reported Outcome Measures in Chronic Neuropathic Pain Clinical Trials − A Systematic Literature Review
Sachau et al.; The Journal of Pain, 24(1): 38
INTEGRATE-Pain: a transatlantic consortium to advance development of effective pain management
Wandner, Laura D et al. Pain medicine (Malden, Mass.), pnad033. 23 Mar. 2023,
The test-retest reliability of large and small fiber nerve excitability testing with threshold tracking
Pia, Hossein et al. Clinical neurophysiology practice vol. 8 71-78. 30 Mar. 2023,
Clinical profiling of specific diagnostic subgroups of women with chronic pelvic pain
Demetriou et al. Front. Reprod. Health, 30 May 2023 Sec. Gynecology Volume 5 – 2023
Comprehensive quantitative sensory testing shows altered sensory function in women with chronic pelvic pain: results from the Translational Research in Pelvic Pain (TRiPP) Study
Coxon, Lydia et al. Pain, 7 Jun. 2023, https://doi.org/10.1097/j.pain.0000000000002955
Leone et al.; Trials (2022) 23:739
Review: Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development
van Nil H et al.; Int. J. Mol. Sci. 23:8295
Identification of Altered Evoked and Non-Evoked Responses in a Heterologous Mouse Model of Endometriosis-Associated Pain
Tejada et al.; Biomedicines 10:501
IMI2 - PainCare - BioPain-RCT1: study protocol for a randomized, double-blind, placebo-controlled, crossover, multi-center trial in healthy subjects to investigate the effects of lacosamide, pregabalin, and tapentadol on biomarkers of pain processing observed by peripheral nerve excitability testing (NET)
Nochi et al.; Trials 23:163
Association of sensory phenotype with quality of life, functionality, and emotional well-being in patients suffering from neuropathic pain
Gierthmühlen et al.; PAIN 163:1378–1387
Pietro et al.; Neurophysiologie Clinique 51_517
Modulation of the N13 component of the somatosensory evoked potentials in an experimental model of central sensitization in humans.
Di Lionardo et al.; Scientific Reports 11:20838
How different experimental models of secondary hyperalgesia change the nociceptive flexion reflex
Leone et al.; Clinical Neurophysiology 132:2989
Preclinical models of endometriosis and interstitial cystitis/bladder pain syndrome: an Innovative Medicines Initiative-PainCare initiative to improve their value for translational research in pelvic pain
Nunez-Badinez et al.; PAIN 2+3(9):2349
Paravertebral block for the prevention of chronic postsurgical pain after breast cancer surgery
Harikouk et al.; Reg Anesth Pain Med 46:251–257.
Developing consensus on core outcome domains for assessing effectiveness in perioperative pain management: results of the PROMPT/IMI-PainCare Delphi Meeting
Pogatzki-Zahn et al. PAIN 162(11):2717
BioPain-RCT3: a randomized, double-blind, placebo-controlled, crossover, multi-center trial in healthy subjects to investigate the effects of lacosamide, pregabalin, and tapentadol on biomarkers of pain processing observed by electroencephalography (EEG)
Mouraux et al.; Trials 22:404
Human surrogate models of central sensitization: A critical review and practical guide
Quesada et al.; Eur J Pain 25(7):1389
González-Cano et al.; Pharmacological Research 155:104724
Developing consensus on core outcome domains and measurement instruments for assessing effectiveness in perioperative pain management after sternotomy, breast cancer surgery, total knee arthroplasty, and surgery related to endometriosis
Kaiser et al.; Trials, 21:773
Dias et al.; Scientific Reports 9:14113, 1
PT221 - Bladder pain induced by chronic stress is mediated by a systemic increase of nerve growth factor involving the activation of adrenoceptors
Dias et al.; Eur Urol Suppl 18(1), e1967
Stouffs et al.
Douleur et analgésie, Volume 31, Numéro 4, Décembre 2018
- 01_PR Setting up and implementing a multiple languages, multi-center PROMs surve (Claudia Weinmann)
- 02_PR Including the patient’s perspective - A systematic literature review of Patient Reported Outcome Measures in chronic neuropathic pain clinical trials (Juliane Sachau, Manon Sendel, Marie Péchard, Kathrin Schnabel, Iris Schmieg, Terkia Medkour, Laurent Ecochard, Markus Woischnik, Hiltrud Liedgens, Esther Pogatzki-Zahn, Ralf Baron, Didier Bouhassira) (IASP22)
- 03_PR Objectively tracked activity is not correlated with patient-reported pain treatment outcomes one week after surgery(Marcus Komann, Claudia Weinmann, Winfried Meißner)
- 04_BP Modulation of Laser Evoked Potentials by Lacosamide, Pregabalin & Tapentadol in Awake Rats (Anthony Blockeel, Anna Sales, Sonya Chapman, Kimberley Jackson, Nicolás Marco-Ariño, Iñaki Trocóniz, Josep-Maria Cendros, Jose Miguel Vela, Anthony Pickering, Andrea Truini, Andre Mouraux, Rolf-Detlef Treede & Keith Phillips)
- 05_BP Characterisation of the neural correlates of central sensitisation induced by the high frequency stimulation (HFS) model in healthy humans using functional magnetic resonance imaging (fMRI) (Sophie Clarke, Vishvarani Wanigasekera, Richard Rogers, Francesca Fardo, Hossein Pia, Zahra Nochi, Nicolas Macian, Vincent Leray, Nanna Brix Finnerup, Gisèle Pickering, André Mouraux, Andrea Truini, Rolf-Detlef Treede and Irene Tracey)
- 06_BP Perception threshold tracking (PTT) - A novel method to assess small fiber function (Hossein Pia, Zahra Nochi, Bernhard Pelz, Marcus Goetz, Jan Hoeink, Rolf-Detlef Treede, Tony Blockeel, Keith Phillips, Nanna Brix Finnerup, Hatice Tankisi)
- 07_BP Does peak alpha-frequency of the resting EEG predict the susceptibility to develop secondary mechanical hyperalgesia? (L. Lebrun, C. Lenoir, E. N. van den Broeke, A. Mouraux)
- 08_BP Investigating the effect of negative expectations on pain and secondary hyperalgesia (S.Gousset, T. Cayrol, M. Papleux, A. Mouraux, E. N. van den Broeke)
- 09_TR Analysis of Rat Ultrasonic Vocalizations in a Preclinical Model for Inflammatory Pain (Paulina Nunez-Badinez, Bianca De Leo, Alexis Laux-Biehlmann, Katy vincent, Jens Nagel)
- 10_TR Exploring pelvic pain and quality of life profiles in the Translational Research in Pelvic Pain (TRiPP) cohort (Lysia Demetriou, Michal Krassowski, Pedro Abreu Mendes, Kurtis Garbutt, Allison Vitonis, Elizabeth Wilkins, Lydia Coxon, Lars Arendt-Nielsen, Qasim Aziz, Judy Birch, Andrew Horne, Anja Hoffman, Lone Hummelshoj, Claire E Lunde, Jane Meijlink, Danielle Perro, Esther Pogatzki-Zahn, Christine Sieberg, Rolf-Detlef Treede, Christian Becker, Franscisco Cruz, Stacey Missmer, Krina Zondervan, Jens Nagel, Katy Vincent)
- 11_TR What drinking water tells us about bladder sensitivity in Chronic Pelvic Pain (Lydia Coxon, Emily Tan, Danielle Perro, Claire Lunde, Joana Ferreira Gomes, Ana Charrua Cordeiro, Pedro Abreu Mendes, Jane Meijlink, Anja Hoffman, Judy Birch, Lone Humnelshoj, Qasim Aziz, Lars Arendt-Nielsen, Esther Pogatzki-Zahn Jan Vollert, Michal Krassowski, Emma Evans, Rolf-Detlef Treede, Lysimachi Demetriou, Stacey Missmer, Andrew Horne, Christine Sieberg, Fransisco Cruz, Jens Nagel, Katy Vincent)
- 12_TR Is conditioned pain modulation (CPM) a useful paradigm in women? A TRiPP study exploring CPM in pain-free women and those living with chronic pelvic pain (Danielle Perro, Lydia Coxon, Claire Lunde, Joana Ferreira Gomes, Ana Charrua, Pedro Abreu Mendes, Lars Arendt-Nielsen, Qasim Aziz, Judy Birch, Lysia Demetriou, Kurtis Garbutt, Andrew Horne, Anja Hoffman, Lone Hummelshoj, Michal Krassowski, Jane Meijlink, Esther Pogatzki-Zahn, Christine Sieberg, Rolf-Detlef Treede, Allison Vitonis, Jan Vollert, Christian Becker, Franscisco Cruz, Christine Sieberg, Stacey Missmer, Krina Zondervan, Jens Nagel, Katy Vincent, on behalf of the TRiPP Consortium)
- 13_TR Understanding Fatigue in Chronic Pelvic Pain patients: a Translational Research in Pelvic Pain (TRiPP) study (Lysia Demetriou, Lydia Coxon, Danielle Perro, Pedro Abreu Mendes, Claire E Lunde, Kurtis Garbutt, Michal Krassowski, Allison Vitonis, Lars Arendt-Nielsen, Qasim Aziz, Judy Birch, Andrew Horne , Anja Hoffman, Lone Hummelshoj, , Jane Meijlink, Danielle Perro, Esther Pogatzki-Zahn, Christine Sieberg, Rolf-Detlef Treede, Christian Becker, Franscisco Cruz, Stacey Missmer, Krina Zondervan, Jens Nagel, Katy Vincent )
- 14_TR Have you ever had a flare of your symptoms? Clinically important findings from under-explored FLARES in Chronic Pelvic Pain (Lydia Coxon, Celia Lugt, Danielle Perro, Claire Lunde, Joana Ferreira Gomes, Ana Charrua Cordeiro, Pedro Abreu Mendes, Judy Birch, Jane Meijlink, Lone Humnelshoj, Anja Hoffmann, Qasim Aziz, Lars Arendt-Nielsen, Esther Pogatzki-Zahn, Jan Vollert, Michal Krassowski, Emma Evans, Rolf-Detlef Treede, Lysimachi Demetriou, Stacey Missmer, Andrew Horne, Christine Sieberg, Fransisco Cruz, Jens Nagel, Katy Vincent)
- 15_TR Widespread pain is associated with poor psychological health, sleep quality, fatigue, and pain catastrophizing in women with chronic pelvic pain: A TRiPP study (Danielle Perro, Lysia Demetriou, Lydia Coxon, Michal Krassowski, Pedro Abreu Mendes, Claire E Lunde, Kurtis Garbutt, Allison Vitonis, Lars Arendt-Nielsen, Qasim Aziz, Judy Birch, Andrew Horne , Anja Hoffman, Lone Hummelshoj, Jane Meijlink, Esther Pogatzki-Zahn, Christine Sieberg, Rolf-Detlef Treede, Christian Becker, Franscisco Cruz, Stacey Missmer, Krina Zondervan, Jens Nagel, Katy Vincent, on behalf of the TRiPP Consortium)
- 16_TR The relationship between pain experience and personality factors in women living with chronic pelvic pain (Emma Evans, Lysia Demetriou, Lydia Coxon, Danielle Perro, Pedro Abreu Mendes, Claire E Lunde, Kurtis Garbutt, Michal Krassowski, Allison Vitonis, Lars Arendt-Nielsen, Qasim Aziz, Judy Birch, Andrew Horne, Anja Hoffman, Lone Hummelshoj, , Jane Meijlink, Esther Pogatzki-Zahn, Christine Sieberg, Rolf-Detlef Treede, Christian Becker, Franscisco Cruz, Stacey Missmer, Krina Zondervan, Jens Nagel, Katy Vincent)
- 17_TR Multi-Center Analysis of Spontaneous Behaviour in Pre-Clinical Models of ENDO using HCA systems (P. Nunez-Badinez et al)
- 18_TR BPS/IC-related to better reproduce urinary bladder changes and pain (Santos-Pereira M, Santos-Leite L, Serrão P, Cruz F, Charrua A)