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Articles by Robert B Raffa
Two Routes to the Same Equation: Kinetic and Statistical-Thermodynamic Derivations of the Classical Drug-Receptor Occupancy Relationship
Specialty Please choose I'm not a medical professional. Allergy and Immunology Anatomy Anesthesiology Biostatistics Cardiac/Thoracic/Vascular Surgery Cardiology Critical Care Dentistry Dermatology Diabetes and Endocrinology Emergency Medicine Epidemiology and Public Health Family Medicine Forensic Medicine Gastroenterology General Practice Genetics Geriatrics Health Policy Hematology HIV/AIDS Hospital-based Medicine I'm not a medical professional.
On the Coexistence of Monitoring and Dampening of Pain Perception During the Fight-or-Flight Response
Specialty Please choose I'm not a medical professional. Allergy and Immunology Anatomy Anesthesiology Biostatistics Cardiac/Thoracic/Vascular Surgery Cardiology Critical Care Dentistry Dermatology Diabetes and Endocrinology Emergency Medicine Epidemiology and Public Health Family Medicine Forensic Medicine Gastroenterology General Practice Genetics Geriatrics Health Policy Hematology HIV/AIDS Hospital-based Medicine I'm not a medical professional.
Combination of the BK-Channel Antagonist ENA-001 and Naloxone Is More Effective Than Either Agent Alone in Reversing Fentanyl-Induced Respiratory Suppression in Rats
Specialty Please choose I'm not a medical professional. Allergy and Immunology Anatomy Anesthesiology Biostatistics Cardiac/Thoracic/Vascular Surgery Cardiology Critical Care Dentistry Dermatology Diabetes and Endocrinology Emergency Medicine Epidemiology and Public Health Family Medicine Forensic Medicine Gastroenterology General Practice Genetics Geriatrics Health Policy Hematology HIV/AIDS Hospital-based Medicine I'm not a medical professional.
Cychlorphine ( N -Propionitrile Chlorphine): An Emerging Benzimidazolone Synthetic Opioid and Its Implications for Overdose Recognition and Management
Back to Journals » Journal of Pain Research » Volume 19 Editorial Opioids and Substance Abuse Authors Raffa RB , Breve F, Pergolizzi JV Jr, Vortsman E, Varrassi G Received 1 May 2026 Accepted for publication 28 June 2026 Published 10 July 2026 Volume 2026:19 620907 DOI https://doi.org/10.2147/JPR.S620907 Checked for plagiarism Yes Editor who approved publication: Dr Timothy Atkinson Robert B Raffa,1,2 Frank Breve,3 Joseph V Pergolizzi Jr,2,4 Eugene Vortsman,5 Giustino Varrassi6 1School of...
A pain memory ‘trace’: cumulative pain perception and damping duri
Back to Journals » Journal of Pain Research » Volume 19 Original Research Behavioral Approaches to Pain Authors Fink W , Raffa RB Received 18 August 2025 Accepted for publication 8 January 2026 Published 21 January 2026 Volume 2026:19 Pages 1—11 DOI https://doi.org/10.2147/JPR.S561278 Checked for plagiarism Yes Review by Single anonymous peer review Peer reviewer comments 2 Editor who approved publication: Dr Jonathan Greenberg Wolfgang Fink,1 Robert B Raffa2,3 1Visual and Autonomous...
Microbiome Alteration Prevents Abstinence-Induced Nicotine Withdrawal in a Well-Established Planarian Model
Specialty Please choose I'm not a medical professional. Allergy and Immunology Anatomy Anesthesiology Biostatistics Cardiac/Thoracic/Vascular Surgery Cardiology Critical Care Dentistry Dermatology Diabetes and Endocrinology Emergency Medicine Epidemiology and Public Health Family Medicine Forensic Medicine Gastroenterology General Practice Genetics Geriatrics Health Policy Hematology HIV/AIDS Hospital-based Medicine I'm not a medical professional.
A Pluripotent Progression of the Gate Control System Theory of Pain – Modeling Ascending & Descending Pain Pathways as a Lotka-Volterra Coupled Control & Feedback Loop
Back to Journals » Journal of Pain Research » Volume 18 Original Research Pre-Clinical/Scientific Authors Fink W , Raffa RB Received 28 February 2025 Accepted for publication 5 August 2025 Published 26 August 2025 Volume 2025:18 Pages 4373—4385 DOI https://doi.org/10.2147/JPR.S525449 Checked for plagiarism Yes Review by Single anonymous peer review Peer reviewer comments 2 Editor who approved publication: Professor E Alfonso Romero-Sandoval Wolfgang Fink,1 Robert B Raffa2 1Visual and...
Postulate of the Existence of a ‘Nocistat’: Rationale and | JPR
Back to Journals » Journal of Pain Research » Volume 18 Authors Raffa RB , Fink W , Tripathi AD Received 21 February 2025 Accepted for publication 7 April 2025 Published 10 April 2025 Volume 2025:18 Pages 1945—1947 DOI https://doi.org/10.2147/JPR.S524175 Checked for plagiarism Yes Editor who approved publication: Dr Michael Schatman Robert B Raffa,1 Wolfgang Fink,2 Anuj D Tripathi2 1Temple University (Emeritus), Philadelphia, PA, USA, and University of Arizona (Adjunct), Tucson, AZ, USA;...
On the Principle and Value of Test Signaling (“Pinging”) i
Back to Journals » Journal of Pain Research » Volume 18 Editorial Pre-Clinical/Scientific Authors Raffa RB , Fink W Received 30 December 2024 Accepted for publication 29 January 2025 Published 12 February 2025 Volume 2025:18 Pages 685—687 DOI https://doi.org/10.2147/JPR.S514929 Checked for plagiarism Yes Editor who approved publication: Professor E Alfonso Romero-Sandoval Robert B Raffa,1 Wolfgang Fink2 1Temple University (Emeritus), Philadelphia, PA, USA, and University of Arizona (Adjunct),...
Letter: Fentanyl-Fold a Flop
As a professor of pharmacology, I note that the recent article about the "fentanyl fold" was replete with errors. For example, the phenomenon is not caused by fentanyl alone, but rather by the combination of fentanyl with xylazine, which is a veterinary tranquilizer (hence the street name "tranq dope", among others).
On Including Pain as an Integral Part of the Fight-or-Flight Response
Back to Journals » Journal of Pain Research » Volume 17 Editorial Behavioral Approaches to Pain Authors Raffa RB, Fink W , Tripathi AD Received 14 October 2024 Accepted for publication 6 November 2024 Published 9 November 2024 Volume 2024:17 Pages 3667—3668 DOI https://doi.org/10.2147/JPR.S500847 Checked for plagiarism Yes Editor who approved publication: Dr Jonathan Greenberg Robert B Raffa,1,2 Wolfgang Fink,3 Anuj D Tripathi3 1Temple University (Emeritus), Philadelphia, PA, USA; 2University...
The Sigma-1 Receptor as a Pharmacologic Chaperone: Energetics
1. Introduction The Sigma-1 receptor (S1R) is a relatively small protein consisting of 223 amino acids, which in humans is encoded by the SIGMAR1 gene located on chromosome 9. The receptor is modeled as having two transmembrane domains with N- and C-terminals both oriented inwards towards the cytosol.
Overdoses due to fentanyl and its analogues (F/FAs) push naloxone to the limit
Abstract What is known and Objective Food and Drug Administration (FDA) risk evaluation and mitigation strategies (REMs) encourage emergency responders, paramedics, law enforcement agents, and even laypeople to be trained in the administration of naloxone with the intent of rescuing individuals from a known or suspected opioid overdose.
Are opioid receptor antagonists adequate for “Opioid” overdose in a changing reality?
Abstract What is known and Objective Deaths due to opioid‐induced respiratory depression (OIRD) continue to rise despite intense regulatory and professional actions. COVID‐19 has only worsened this situation.1 An opioid receptor antagonist (ORA) such as naloxone is the most common intervention for OIRD. However, with increasing overdose from highly potent illicit opioids and polysubstance abuse, appraisal of the adequacy of ORA seems warranted and timely.
The problem of postoperative respiratory depression
Abstract What is known and Objective Postsurgical recovery is influenced by multiple pre‐, intra‐ and perioperative pharmacotherapeutic interventions, including the administration of medications that can induce respiratory depression postoperatively. We present a succinct overview of the topic, including the nature and magnitude of the problem, contributing factors, current limited options, and potential novel therapeutic approach.
A Q&A with Robert B. Raffa
What inspired you to do what you do? I have been extremely lucky to be able to mostly do what I enjoy doing, and to have parents who allowed it, even when they didn’t understand what I was doing or why (and maybe I didn’t either). My mother gave us an interest in all things, particularly in the creative—mine and my brother’s turned to science, my sister’s to art. My father kept it real and obtainable. In my 2nd grade classroom, I couldn’t wait to go home.
The conundrum of polysubstance overdose
Abstract What is known and objective Treating an opioid overdose using an opioid receptor antagonist (such as naloxone) makes mechanistic sense and can be effective. Unfortunately, the majority of current drug overdose deaths involve polysubstance use (i.e., an opioid plus a non‐opioid). Comment Respiratory depression induced by opioids results from excessive opioid molecules binding to opioid receptors. This effect can be reversed by an opioid receptor antagonist.
Common Opioid-Drug Interactions: What Clinicians Need to Know
The overall prevalence of drug–drug interactions in patients on long-term opioids is 27%. Good pain management practice should include knowledge of potential interactions, and well as ways to avoid and ameliorate them. By Joseph V. Pergolizzi, MD and Robert B. Raffa, PhD Patients who require opioid medications often present with comorbidities or disease sequelae related to their pain condition. These patients frequently require medications in addition to their opioid pain medications.
Benzodiazepines: Thinking outside the black box
Abstract What is known and Objective The United States Food and Drug Administration (FDA) recently issued a Drug Safety Communication requiring Boxed Warning updating and other changes in order to improve the safe use of the benzodiazepine drug class. These changes were prompted because ‘The current prescribing information for benzodiazepines does not provide adequate warnings about [the] serious risks and harms associated with these medicines so they may be prescribed and used inappropriately’.
Bone fractures during the time of coronavirus
1 WHAT IS KNOWN AND OBJECTIVE The name coronavirus derives from the image created in electron micrographs, which is reminiscent of the solar corona.1, 2 Coronaviruses have variable propensities to infect humans, but in December 2019 a pneumonia outbreak occurred in Wuhan China that was soon traced to a novel strain.3 The World Health Organization (WHO) assigned the temporary name 2019‐nCoV4; later renamed SARS‐CoV‐2 by the International Committee on Taxonomy of Viruses.
Developments in combined analgesic regimens for improved safety in postoperative pain management
FDA drug safety communication: FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children; recommends against use in breastfeeding women Rockville, Maryland Food and Drug Administration .: Food and Drug Administration;. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-restricts-use-prescription-codeine-pain-and-cough-medicines-and
Developments in combined analgesic regimens for improved safety in postoperative pain management
ABSTRACT Introduction: Fixed-dose combination analgesic regimens may be similarly effective to opioid monotherapy but with potentially less risk. A number of individualized combination regimens can be created, including nonopioid agents such as acetaminophen and nonsteroidal anti-inflammatory drugs, opioids, and adjunctive agents such as gabapentin, pregabalin, and muscle relaxants. Areas covered: When such combinations have a synergistic effect, analgesic benefits may be enhanced.
Opioid withdrawal symptoms, a consequence of chronic opioid use and opioid use disorder: Current understanding and approaches to management
Abstract What is known and objective Opioid use in the United States has reached unprecedented—some would even say crisis—levels. Although many individuals use opioid drugs as part of legitimate pain management plans, a significant number misuse prescription or illicit opioids. With regular opioid use, individuals develop tolerance and physical dependence; both are predictable, physiologic responses to repeated opioid exposure.
Treating pain in patients with dementia and the possible concomitant relief of symptoms of agitation
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.
Treating opioid‐induced constipation in patients taking other medications: Avoiding CYP450 drug interactions
Summary What is known and objective When patients fail other treatment regimens and still suffer from pain sufficiently severe, opioid analgesics are appropriate and required. Unfortunately, constipation is a common adverse effect of opioids. Opioid‐induced constipation (OIC) can be treated with one of the new peripherally acting µ‐opioid receptor antagonist (PAMORA) agents.
Journal of Clinical Pharmacy and Therapeutics
1 WHAT IS KNOWN AND OBJECTIVE The legislature of the State of Hawaii of the United States touched off a firestorm of controversy with a decision to ban the two most commonly used sunscreen agents. The intent of the legislation is protection of coral reefs.1 The ban goes into effect in Hawaii on January 1, 2021, but proponents predict that similar bans will soon spread to other areas of the world that have coral reefs (Figure 1).
Discovery of “folded DNA” structures in human cells: Potential drug targets
What is known and objective The double‐helical conformation of human DNA (hDNA) is so axiomatic that it is called the “canonical” form. Recently, though, intrastrand folds (“I‐motifs” and “G‐quadruplexes”) have been identified in hDNA. These could be targets for novel drug discovery. Any interruption of the canonical form of hDNA fundamentally impacts the normal progression of transduction and translation.
Considering tapentadol as a first-line analgesic: 14 questions
Tapentadol is the newest centrally acting analgesic to be approved by the US FDA and regulatory bodies in other countries. It has been called the first-in-class of a novel-acting analgesic mechanism of action that combines Â?-opioid receptor agonist activity with neuronal norepinephrine-reuptake inhibition in a single molecule.
Is Buprenorphine a ‘Partial Agonist’? Preclinical and Clinical Evidence
Buprenorphine has a unique pharmacological profile, and while much remains to be learned, it is clear that it is an important treatment option for the management of moderate to severe cancer and non-cancer pain syndromes By Robert B. Raffa, PhD and Joseph V. Pergolizzi, Jr., MD It has become commonplace for buprenorphine to be referred to as a ‘partial agonist,’ with no reason given.
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