Article
Biochemistry & Molecular Biology
Milena Sleczkowska, Rowida Almomani, Margherita Marchi, Bianca T. A. de Greef, Maurice Sopacua, Janneke G. J. Hoeijmakers, Patrick Lindsey, Erika Salvi, Gidon J. Boenhof, Dan Ziegler, Rayaz A. Malik, Stephen G. Waxman, Giuseppe Lauria, Catharina G. Faber, Hubert J. M. Smeets, Monique M. Gerrits
Summary: Neuropathic pain is common in diabetic peripheral neuropathy (DN), and it may be caused by pathogenic ion channel gene variants. Variants in ion channel genes were found in DN patients with and without pain, suggesting their role in pain generation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Rowida Almomani, Maurice Sopacua, Margherita Marchi, Milena Sleczkowska, Patrick Lindsey, Bianca T. A. de Greef, Janneke G. J. Hoeijmakers, Erika Salvi, Ingemar S. J. Merkies, Maryam A. Ferdousi, Rayaz Malik, Dan Ziegler, Kasper W. J. Derks, Gidon Boenhof, Filippo Martinelli-Boneschi, Daniele Cazzato, Raffaella Lombardi, Sulayman G. Dib-Hajj, Stephen Waxman, Hubert J. M. M. Smeets, Monique G. Gerrits, Catharina Faber, Giuseppe Lauria
Summary: Rare SCG genetic variants may contribute to the development of painful neuropathy. Genetic profiling and SCG variant identification can provide better understanding of the genetic variability in patients with painful and painless neuropathy, leading to improved risk stratification and personalized pain treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Mayank Gupta, Nebojsa Nick Knezevic, Alaa Abd-Elsayed, Mahoua Ray, Kiran Patel, Bhavika Chowdhury
Summary: Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus that significantly impacts quality of life. Various pharmacological options such as anticonvulsants, antidepressants, and topical capsaicin, as well as the recently approved tapentadol, are recommended for managing PDN. In addition to pharmacotherapy, neuromodulation therapies such as intrathecal therapy, TENS, and SCS have shown success in providing pain relief for PDN patients.
Article
Clinical Neurology
Alise Kalteniece, Maryam Ferdousi, Shazli Azmi, Saif Ullah Khan, Anne Worthington, Andrew Marshall, Catharina G. Faber, Giuseppe Lauria, Andrew J. M. Boulton, Handrean Soran, Rayaz A. Malik
Summary: This study showed that corneal nerve loss increases with the severity of neuropathic pain, and corneal nerve density may be correlated with the diagnosis of PDN.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Eleonora Galosi, Giuseppe Di Pietro, Silvia La Cesa, Giulia Di Stefano, Caterina Leone, Alessandra Fasolino, Andrea Di Lionardo, Frida Leonetti, Raffaella Buzzetti, Cristina Mollica, Giorgio Cruccu, Andrea Truini
Summary: The study found that diabetic polyneuropathy mainly manifests as mixed-fiber polyneuropathy, simultaneously involving A beta, A delta, and C-fibers. In most patients, neuropathic pain is distinctly associated with small-fiber damage.
Article
Endocrinology & Metabolism
Jackie Elliott, Gordon Sloan, Lynda Stevens, Dinesh Selvarajah, Giorgio Cruccu, Rajiv A. Gandhi, Peter Kempler, John H. Fuller, Nishi Chaturvedi, Solomon Tesfaye
Summary: This study analyzed the EURODIAB Prospective Complications Study data to investigate the incidence and risk factors of painful DPN. It found that female sex was a risk factor for painful DPN and there was less evidence of diabetic nephropathy in painful DPN cases.
Article
Anesthesiology
Dale George, Sandra Hackelberg, Nirupa Jayaraj, Dongjun Ren, Seby Edaserry, Craig Rathwell, Rachel Miller, Jeffery Savas, Richard Miller, Daniela Maria Menichella, Anne-Marie Malfait
Summary: This research identified elevated mitochondrial fission proteins and increased calcium signaling in dorsal root ganglion (DRG) neurons in a mouse model of painful diabetic neuropathy (PDN). By selectively deleting the mitochondrial calcium uniporter, the study demonstrated the restoration of normal mitochondrial morphology, prevention of axonal degeneration, and reversal of mechanical allodynia in the PDN mouse model. These findings indicate the potential of targeting calcium entry into nociceptor mitochondria as an effective therapeutic approach for PDN.
Review
Biochemistry & Molecular Biology
Milena Sleczkowska, Kaalindi Misra, Silvia Santoro, Monique M. Gerrits, Janneke G. J. Hoeijmakers, PainNet Study Grp
Summary: This study discusses the potential role of various peripheral ion channels involved in sensory signaling, neuronal excitation regulation, involuntary action potential generation, thermal pain, pH modulation, and neurotransmitter release related to painful neuropathy, as well as their prospective role as therapeutic targets.
Article
Neurosciences
D. F. S. Santos, R. R. Donahue, D. E. Laird, M. C. G. Oliveira, B. K. Taylor
Summary: Females exhibit greater anti-hyperalgesic responses to Pioglitazone in mouse models of chronic pain, suggesting the potential analgesic properties of Pioglitazone in a broad spectrum of chronic pain conditions, especially in women.
Article
Biochemistry & Molecular Biology
Milena Sleczkowska, Rowida Almomani, Margherita Marchi, Erika Salvi, Bianca T. A. de Greef, Maurice Sopacua, Janneke G. J. Hoeijmakers, Patrick Lindsey, Stephen G. Waxman, Giuseppe Lauria, Catharina G. Faber, Hubert J. M. Smeets, Monique M. Gerrits
Summary: This study assessed the role of fifteen ion channel genes in neuropathic pain. Variants in ion channel genes were identified in SFN patients, with TRP genes being the most frequent. Patients with these variants reported more severe pain. This study provides promising gene candidates for future research on neuropathic pain etiology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Clinical Neurology
Josianna Henson, Narayana C. Varhabhatla, Zvonimir Bebic, Alan D. Kaye, R. Jason Yong, Richard D. Urman, Justin S. Merkow
Summary: Painful diabetic neuropathy is a common disease causing significant pain and disability. Spinal cord stimulation has shown moderate-quality evidence for safety and efficacy in treating this condition. Further high-quality research, including large-scale randomized controlled trials, is needed to confirm its effectiveness.
Article
Anesthesiology
Andrew S. C. Rice, Robert H. Dworkin, Nanna B. Finnerup, Nadine Attal, Praveen Anand, Roy Freeman, Alessandro Piaia, Francesca Callegari, Christie Doerr, Subhayan Mondal, Nisha Narayanan, Laurent Ecochard, Yanina Flossbach, Shaloo Pandhi
Summary: The analgesic efficacy and safety of EMA401 in patients with postherpetic neuralgia and painful diabetic neuropathy were assessed in two phase 2b studies, showing consistent clinical improvement in pain intensity reduction. However, premature termination of the studies prevented definitive conclusions from being drawn.
Article
Anesthesiology
Marko S. Todorovic, Karen Frey, Robert A. Swarm, Michael Bottros, Lesley Rao, Danielle Tallchief, Kristin Kraus, Kathleen Meacham, Kristopher Bakos, Xiaowei Zang, Jong Bong Lee, Leonid Kagan, Simon Haroutounian
Summary: Intravenous lidocaine can alleviate painful diabetic peripheral neuropathy (DPN), but quantitative sensory testing (QST) cannot predict treatment response.
CLINICAL JOURNAL OF PAIN
(2022)
Article
Clinical Neurology
Mirna Andelic, Erika Salvi, Stefania Marcuzzo, Margherita Marchi, Raffaella Lombardi, Daniele Cartelli, Daniele Cazzato, Elkadia Mehmeti, Andrea Gelemanovic, Matilde Paolini, Carlotta Pardo, Ilaria D'Amato, Janneke G. J. Hoeijmakers, Sulayman Dib-Hajj, Stephen G. Waxman, Catharina G. Faber, Giuseppe Lauria
Summary: Personalized management of neuropathic pain is a clinical need that has not been fulfilled due to various factors. Recent studies on microRNA have provided insights into pain-related mechanisms and identified potential drug candidates. By generating a molecular profile of the epidermis in patients with sodium channel-related painful neuropathy, the researchers identified specific miRNAs and mRNA targets that are involved in peripheral sensory transduction and modulation. The findings suggest a complex interaction between epidermal cells and axons in neuropathy pain. This targeted molecular profiling could advance personalized medicine for neuropathic pain.
Article
Neurosciences
Vikram Thakur, Mayra A. Gonzalez, Maria Parada, Robert D. Martinez, Munmun Chattopadhyay
Summary: Diabetic painful neuropathy is a severe complication of diabetes, and alterations in neuroinflammatory mediators play a crucial role in its development. This study suggests that using the HDAC inhibitor FK228 can suppress NETosis and improve diabetic nerve degeneration in DPN patients.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Medicine, General & Internal
T. Keller, R. Freynhagen, T. R. Toelle, I. Liwowsky, P. Moeller, P. Huellemann, U. Gockel, E. Stemmler, R. Baron
CURRENT MEDICAL RESEARCH AND OPINION
(2016)
Article
Anesthesiology
P. Marchettini, S. Wilhelm, H. Petto, S. Tesfaye, T. Toelle, D. Bouhassira, R. Freynhagen, G. Cruccu, A. Lledo, E. Choy, E. Kosek, J. A. Mico, M. Spaeth, V. Skljarevski, A. Lenox-Smith, S. Perrot
EUROPEAN JOURNAL OF PAIN
(2016)
Review
Clinical Neurology
Rainer Freynhagen, Miroslav Backonja, Stephan Schug, Gavin Lyndon, Bruce Parsons, Stephen Watt, Regina Behar
Article
Genetics & Heredity
D. Kringel, A. Ultsch, M. Zimmermann, J-P Jansen, W. Ilias, R. Freynhagen, N. Griessinger, A. Kopf, C. Stein, A. Doehring, E. Resch, J. Loetsch
PHARMACOGENOMICS JOURNAL
(2017)
Article
Anesthesiology
Philipp Huellemann, Thomas Keller, Maria Kabelitz, Rainer Freynhagen, Thomas Toelle, Ralf Baron
Article
Anesthesiology
Ralf Baron, Christoph Maier, Nadine Attal, Andreas Binder, Didier Bouhassira, Giorgio Cruccu, Nanna B. Finnerup, Maija Haanpaa, Per Hansson, Philipp Huellemann, Troels S. Jensen, Rainer Freynhagen, Jeffrey D. Kennedy, Walter Magerl, Tina Mainka, Maren Reimer, Andrew S. C. Rice, Marta Segerdahl, Jordi Serra, Soren Sindrup, Claudia Sommer, Thomas Toelle, Jan Vollert, Rolf-Detlef Treede
Article
Anesthesiology
Annette Christoph, Marie-Henriette Eerdekens, Maurits Kok, Gisela Volkers, Rainer Freynhagen
Article
Anesthesiology
Jan Vollert, Christoph Maier, Nadine Attal, David L. H. Bennett, Didier Bouhassira, Elena K. Enax-Krumova, Nanna B. Finnerup, Rainer Freynhagen, Janne Gierthmuehlen, Maija Haanpaa, Per Hansson, Philipp Hullemann, Troels S. Jensen, Walter Magerl, Juan D. Ramirez, Andrew S. C. Rice, Sigrid Schuh-Hofer, Marta Segerdahl, Jordi Serra, Pallai R. Shillo, Soeren Sindrup, Solomon Tesfaye, Andreas C. Themistocleous, Thomas R. Toelle, Rolf-Detlef Treede, Ralf j Baron
Review
Medicine, General & Internal
R. Freynhagen, C. Elling, T. Radic, M. Sohns, H. Liedgens, D. James, R. McCool, M. Edwards
Summary: This study aimed to assess the relative safety of oral tapentadol PR and other opioid analgesics for moderate or severe chronic pain in adults through a systematic review and network meta-analysis. The evidence from RCTs suggested that tapentadol is associated with relatively lower odds of adverse events compared to most active comparators. However, the data from withdrawal trials were less clear with higher uncertainty around the results and appeared to contradict the RCT evidence.
CURRENT MEDICAL RESEARCH AND OPINION
(2021)
Article
Medicine, General & Internal
Rainer Freynhagen, Roberto Rey, Charles Argoff
CURRENT MEDICAL RESEARCH AND OPINION
(2020)
Article
Medicine, General & Internal
Leila Ghamkhar, S. Mohaddesseh Saghaeian, Hoda Niknam, Seyed-Masoud Hashemi, Rainer Freynhagen, Amir H. Kahlaee
Summary: The objective of this study was to translate and adapt the painDETECT questionnaire into Persian, resulting in the reliable Persian version P-PDQ. The P-PDQ showed good internal consistency, test-retest reliability, and significant correlation with validated measures, making it a valuable tool in identifying neuropathic components in chronic pain cases.
CURRENT MEDICAL RESEARCH AND OPINION
(2021)
Article
Anesthesiology
Jessica Pinto Martins do Rio, Juliana Valentim Bittencourt, Leticia Amaral Correa, Rainer Freynhagen, Felipe Jose Jandre dos Reis, Tamiris Barbosa de Melo, Diego Galace, Leandro Alberto Calazans Nogueira
Summary: The study translated and cross-culturally adapted the painDETECT questionnaire into Brazilian Portuguese, with good internal consistency for identifying neuropathic components in pain among Brazilian patients.
BRAZILIAN JOURNAL OF ANESTHESIOLOGY
(2022)
Article
Anesthesiology
Janne Gierthmuehlen, Johann Boehmer, Nadine Attal, Didier Bouhassira, Rainer Freynhagen, Maija Haanpaa, Per Hansson, Troels Staehelin Jensen, Jeffrey Kennedy, Christoph Maier, Andrew S. C. Rice, Juliane Sachau, Marta Segerdahl, Soren Sindrup, Thomas Toelle, Rolf-Detlef Treede, Lise Ventzel, Jan Vollert, Ralf Baron
Summary: Neuropathic pain patients can be categorized into sensory loss, mechanical hyperalgesia, and thermal hyperalgesia phenotypes, which have different impacts on mental health, functionality, and quality of life. Sensory loss patients experience higher pain interference, lower self-reported health state, and more problems with mobility, usual activities, and self-care compared to thermal hyperalgesia patients. These results suggest that the somatosensory phenotype should be considered for personalized pain management.
Article
Medicine, General & Internal
R. Baron, R. D. Treede, F. Birklein, T. Cegla, R. Freynhagen, M. L. Heskamp, K. U. Kern, C. Maier, R. Rolke, S. Seddigh, C. Sommer, S. Staender, C. Maihoefner
CURRENT MEDICAL RESEARCH AND OPINION
(2017)
Review
Anesthesiology
M. R. Mulvey, E. G. Boland, D. Bouhassira, R. Freynhagen, J. Hardy, M. J. Hjermstad, S. Mercadante, C. Perez, M. I. Bennett
BRITISH JOURNAL OF ANAESTHESIA
(2017)