Open-Label Placebo (OLP): Take This, It Is A Sugar Pill, It Will Help You!

When Lee D. Park, M.D. and Uno Covi, M.D. from the Department of Psychiatry at Johns Hopkins University School of Medicine in Baltimore, MD, back in the 1960s, gave their depressed patients placebos, they did exactly this — told them that the pill did not contain an active pharmacological agent (at that time, likely a classical tricyclic antidepressant), but was a placebo. They were surprised to see that it did work (1): 14 of their 15 patients reported improved symptoms a week later, and no difference was found between those that had believed they were taking the placebo and those that had — upon questioning — believed they had received a real drug.

Placebo Effects: Biological, Clinical and Ethical Advances

For many years, placebos have been conceptualized by their inert content and their use as controls in clinical trials and treatments in clinical practice. Recent research demonstrates that placebo effects are genuine psychobiological phenomenon attributable to the overall therapeutic context, and that placebo effects can be robust in both laboratory and clinical settings. Evidence has …

How Pain Works

Let's say that you stub your toe. Nerves in the toe known as nociceptors, tasked with sensing pain, go into action. They send messages to the spinal cord that pain has occurred; the worse the stub, the more rapidly and powerfully they fire. The spinal cord then releases neurotransmitters to the brain's thalamus, communicating with the …

An Introduction of Pain Pathways and Mechanisms

​This article provides an overview of the physiological mechanisms of pain and the important pain pathways. We will discuss pain receptors, transmission of pain signals to the spinal cord and pain pathways within the spinal cord. We will also look at how pain can be modulated at different levels along the pathway. Finally we discuss different types of pain including visceral and neuropathic pain.

The 3 Basic Types of Pain

There are two main classifications of pain: the commonsensical sort that arises from damaged tissue (nociceptive pain), and the more exotic kind that comes from damage to the system that reports and interprets damage, the nervous system (neuropathic pain). This is the difference between engine trouble and trouble with that light on your dashboard that claims there’s engine trouble. Oddly, there is still no official …

Phantom Limb Pain: Mechanisms and Treatment Approaches

The vast amount of research over the past decades has significantly added to our knowledge of phantom limb pain. Multiple factors including site of amputation or presence of pre-amputation pain have been found to have a positive correlation with the development of phantom limb pain. The paradigms of proposed mechanisms have shifted over the past years from the psychogenic theory to peripheral and central neural changes involving cortical reorganization. More recently, the role of mirror neurons in the brain has been proposed in the generation of phantom pain. A wide variety of treatment approaches have been employed, but mechanism-based specific treatment guidelines are yet to evolve. Phantom limb pain is considered a neuropathic pain, and most treatment recommendations are based on recommendations for neuropathic pain syndromes. Mirror therapy, a relatively recently proposed therapy for phantom limb pain, has mixed results in randomized controlled trials. Most successful treatment outcomes include multidisciplinary measures. This paper attempts to review and summarize recent research relative to the proposed mechanisms of and treatments for phantom limb pain.

Mechanisms of Pain

Persistent or chronic pain is the primary reason people seek medical care, yet current therapies are either inadequate for certain types of pain or cause intolerable side effects. Recently, pain neurobiologists have identified a number of cellular and molecular processes that lead to the initiation and maintenance of pain. Understanding these underlying mechanisms has given significant promise for the development of more effective, more specific pain therapies in the near future.

Learned Immunosuppressive Placebo Responses in Renal Transplant Patients

Akin to other physiological responses, immune functions can be modified in humans through associative conditioning procedures as part of a learned placebo response. However, it is unclear whether learned immune responses can be produced in patient populations already receiving an immunosuppressive regimen. In the present study, we demonstrate in renal transplant patients who were already receiving immunosuppressive treatment that learned immunosuppressive placebo responses increased efficacy of immunosuppressive medication. These data demonstrate that behavioral conditioning of drug responses may be a promising tool that could be used as a placebo-based dose-reduction strategy in an ongoing immunopharmacological regimen, the aim being to limit unwanted drug adverse effects and to improve treatment efficacy.

Nonconscious Activation of Placebo and Nocebo Pain Responses

The dominant theories of human placebo effects rely on a notion that consciously perceptible cues, such as verbal information or distinct stimuli in classical conditioning, provide signals that activate placebo effects. However, growing evidence suggest that behavior can be triggered by stimuli presented outside of conscious awareness. Here, we performed two experiments in which the responses to thermal pain stimuli were assessed. The first experiment assessed whether a conditioning paradigm, using clearly visible cues for high and low pain, could induce placebo and nocebo responses. The second experiment, in a separate group of subjects, assessed whether conditioned placebo and nocebo responses could be triggered in response to nonconscious (masked) exposures to the same cues. A total of 40 healthy volunteers (24 female, mean age 23 y) were investigated in a laboratory setting. Participants rated each pain stimulus on a numeric response scale, ranging from 0 = no pain to 100 = worst imaginable pain. Significant placebo and nocebo effects were found in both experiment 1 (using clearly visible stimuli) and experiment 2 (using nonconscious stimuli), indicating that the mechanisms responsible for placebo and nocebo effects can operate without conscious awareness of the triggering cues. This is a unique experimental verification of the influence of nonconscious conditioned stimuli on placebo/ nocebo effects and the results challenge the exclusive role of awareness and conscious cognitions in placebo responses.