TY - JOUR
T1 - Bridging the translational gap
T2 - adenosine as a modulator of neuropathic pain in preclinical models and humans
AU - Arendt-Nielsen, Lars
AU - Klitgaard, Henrik
AU - Hansen, Stine N.
N1 - The team at Aalborg University Library are acknowledged for their help with the bibliometric analysis (J T Pedersen, S Dreier, A L Høj, L Thomsen).
PY - 2024/1
Y1 - 2024/1
N2 - Objectives: This review aims to analyse the published data on preclinical and human experimental and clinical adenosine modulation for pain management. We summarise the translatability of the adenosine pathway for further drug development and aim to reveal subgroups of pain patients that could benefit from targeting the pathway. Content: Chronic pain patients suffer from inadequate treatment options and drug development is generally impaired by the low translatability of preclinical pain models. Therefore, validating the predictability of drug targets is of high importance. Modulation of the endogenous neurotransmitter adenosine gained significant traction in the early 2000s but the drug development efforts were later abandoned. With the emergence of new drug modalities, there is a renewed interest in adenosine modulation in pain management. In both preclinical, human experimental and clinical research, enhancing adenosine signalling through the adenosine receptors, has shown therapeutic promise. A special focus has been on the A
1 and A
3 receptors both of which have shown great promise and predictive validity in neuropathic pain conditions. Summary: Adenosine modulation shows predictive validity across preclinical, human experimental and clinical investigations. The most compelling evidence is in the field of neuropathic pain, where adenosine has been found to alleviate hyperexcitability and has the potential to be disease-modifying. Outlook: Adenosine modulation show therapeutic potential in neuropathic pain if selective and safe drugs can be developed. New drug modalities such as RNA therapeutics and cell therapies may provide new options.
AB - Objectives: This review aims to analyse the published data on preclinical and human experimental and clinical adenosine modulation for pain management. We summarise the translatability of the adenosine pathway for further drug development and aim to reveal subgroups of pain patients that could benefit from targeting the pathway. Content: Chronic pain patients suffer from inadequate treatment options and drug development is generally impaired by the low translatability of preclinical pain models. Therefore, validating the predictability of drug targets is of high importance. Modulation of the endogenous neurotransmitter adenosine gained significant traction in the early 2000s but the drug development efforts were later abandoned. With the emergence of new drug modalities, there is a renewed interest in adenosine modulation in pain management. In both preclinical, human experimental and clinical research, enhancing adenosine signalling through the adenosine receptors, has shown therapeutic promise. A special focus has been on the A
1 and A
3 receptors both of which have shown great promise and predictive validity in neuropathic pain conditions. Summary: Adenosine modulation shows predictive validity across preclinical, human experimental and clinical investigations. The most compelling evidence is in the field of neuropathic pain, where adenosine has been found to alleviate hyperexcitability and has the potential to be disease-modifying. Outlook: Adenosine modulation show therapeutic potential in neuropathic pain if selective and safe drugs can be developed. New drug modalities such as RNA therapeutics and cell therapies may provide new options.
KW - adenosine
KW - neuropathic pain
KW - translation
KW - animal models
KW - human studies
UR - http://www.scopus.com/inward/record.url?scp=85179929505&partnerID=8YFLogxK
U2 - 10.1515/sjpain-2023-0048
DO - 10.1515/sjpain-2023-0048
M3 - Review article
SN - 1877-8860
VL - 24
JO - Scandinavian Journal of Pain
JF - Scandinavian Journal of Pain
IS - 1
M1 - 20230048
ER -