Placebo-Induced Changes in Spinal Cord Pain Processing

Abstract

Pain is an essential sensory modality, signaling injury or threat of injury. Pain perception depends on both biological and psychological factors. However, it is not known whether psychological factors modify spinal mechanisms or if its effect is limited to cortical processing. Here, we use a placebo analgesic model to show that psychological factors affect human spinal nociceptive processes. Mechanical hyperalgesia (hypersensitivity) after an injury is attributable to sensitized sensory neurons in the spinal cord. After a 5 min, 46°C heating of the skin, subjects developed areas of mechanical hyperalgesia. This area was smaller in a placebo condition compared with a baseline condition. This result suggests that placebo analgesia affects the spinal cord as well as supra-spinal pain mechanisms in humans and provides strong supporting evidence that placebo analgesia is not simply altered reporting behavior. Central sensitization is thought to mediate the exaggerated pain after innocuous sensory stimulation in several clinical pain conditions that follow trauma and nervoussystem injury. These new data indicate that expectation about pain and analgesia is an important component of the cognitive control of central sensitization.

Placebo effects on human μ-opioid activity during pain

“…Consistent with behavioral studies (7,11,40), the results indicate that placebo treatment induces increases in endogenous opioid activity in -opioid-rich limbic and paralimbic regions, including PAG, NCF, DRN, OFC, amygdala, two dissociable regions of the anterior cingulate (rACC and pgACC), ventral aINS, and thalamus. All of these regions have shown a response to placebo or expectancy effects in pain or pharmacological administration of opioids.…”

Placebo response to manual therapy: something out of nothing?

“…54,55 Additionally, the placebo effect is significantly lessened in patients with Alzheimer's disease with pre-frontal cortex involvement 56 and can be abolished with experimental disruption of the prefrontal cortex through transcranial magnetic stimulation. 57 Beyond a specific supraspinal mechanism, more recent imaging studies demonstrate spinal cord-related responses to placebo 58,59 and suggest that placebo may modulate pain throughout the continuum of the nervous system. Placebo-related hypoalgesia may be quite specific and localized to the expected site while not present in regions separate from the area of application.…”

Opioid-Mediated Placebo Responses Boost Pain Endurance and Physical Performance: Is It Doping in Sport Competitions?

“…The recent advances in the neurobiology of the placebo effect have shown that the administration of a placebo (inert substance), along with verbal suggestions of clinical benefit, activates different neurotransmitters in the brain, like endogenous opioids (Levine et al, 1978;Amanzio and Benedetti, 1999;Zubieta et al, 2005;Wager et al, 2007) and dopamine (de la Fuente-Fernandez et al, 2001;Strafella et al, 2006), and is associated to neural changes at both the cortical and subcortical level (Petrovic et al, 2002;Benedetti et al, 2004;Wager et al, 2004;Kong et al, 2006;Matre et al, 2006;Price et al, 2007). Powerful placebo responses can be obtained after pharmacological preconditioning, whereby the repeated administration of a drug is replaced with an inert substance (Ader and Cohen, 1982;Benedetti et al, 2005;Colloca and Benedetti, 2005;Pacheco-Lopez et al, 2006).…”