“Nature has placed mankind under the governance of two sovereign masters; pain and pleasure,” Jeremy Bentham.
The pursuit of pleasure and the avoidance of pain is one of the first principles of animal life. So it seems fitting that researchers have spent decades mapping the internal structure of the brain’s reward system. Of course, humans through the ages have known that pleasure is obtained via sexual stimulation or the enjoyment of a good meal. However, we have only begun to appreciate the important role that the brain plays as a mediator in the experience of somatic pleasure.
In 1954, James Olds and Peter Milner placed electrodes into the brains of rats and gave them the option of pushing a lever, which would send an electric pulse through the electrode to stimulate the brain. Although their experiment did not target a specific brain region, they found that some rats pressed the lever thousands of times an hour so that the electrical impulses would continue. Some rats even pressed the lever so many times that they lost interest in food and sex, and eventually died from dehydration and exhaustion. It seemed that the electrical stimulation of certain brain regions could activate a sense of pleasure or euphoria in the rats powerful enough to turn their attention away from other stimuli (Olds, 1956).
The advent of in vivo microdialysis in the 1960’s made it possible for scientists to measure the concentration various neurotransmitters in the extracellular space of animal brains. Initial studies showed that the neurotransmitter dopamine (DA) was associated with rewarding activities such as food, sex, and the neutral stimuli that became associated with them (Shultz, et al., 1993; Arias-Carrion, 2007). A subsequent study conducted by Fiorino et al. (1993) used in vivo microdialysis to measure concentrations of extracellular dopamine in the nucleus accumbens (NAc) of freely-moving rats before, during, and after the ventral tegmental area (VTA) was stimulated by an implanted electrode. Although this study was not the first of its kind, it showed that DA concentrations in the NAc were increased by about 185% after high-intensity electrical stimulation of the VTA.
While electrical stimulation seemed to have a remarkable effect on extracellular dopamine concentrations (Phillips, 1992), even more striking results were obtained via intravenous administration of cocaine, which increased basal dopamine concentrations by 464% on average (Pettit, 1990). Other substances of abuse such as cannabinoids, nicotine, phenylcyclidine, and amphetamines are all known to have a similar effect on mesolimbic and mesocortical dopamine (Hyman et al., 2006). However benign substances such as chocolate or chili peppers can also increase dopamine concentrations (Volkow et al., 1996). All of these substances can create pleasure or euphoria by increasing dopamine levels, however, there are many drugs that do the opposite. One of the classic side-effects patients with schizophrenia complain of is anhedonia, or a decreased sense of enjoyment or motivation for their usual activities (Pizzagalli, 2010). Antipsychotic medications help to decrease positive symptoms by blocking dopamine receptors throughout the brain, but unfortunately, this suppression of this neurotransmitter is also thought to drive symptoms of anhedonia (Wise, 2008).
Pain, which is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage”(Bonica, 1979, p.4) is traditionally thought of as the opposite of pleasure. However, the mechanisms by which they are processed seem to be related.
Nociceptive pain, felt when we stub a toe or scrape a knee, is mediated by two afferent pathways with corresponding receptors. The first are Aδ receptors, which are myelinated nerve fibers of medium diameter that rapidly conduct their signal to the brain along the neospinothalamic tract. This tract terminates in the thalamus but also has secondary projections to the somatosensory cortex (Backonja, 1996). The second are the C-fibers, which are unmyelinated neurons that conduct their impulses more slowly through the paleospinothalamic tract. Signals from these fibers give rise to slow, chronic pain and are processed in the brainstem, thalamus, and periaqueductal gray (PAG) (Basbaum and Jessell, 2000; Basbaum, 2009).
Although scientists have come to know much about pain perception in the last several decades, people all over the world have been using opioids to attenuate pain for centuries. Morphine, which was first synthesized nearly two hundred years ago, is the most powerful analgesic in contemporary medicine, yet its mechanism was long unclear. In 1996, Hans Matthes and colleagues administered morphine to genetically altered “knockout” mice lacking µ-receptors and found that doses of morphine had no effect on analgesia or withdrawal symptoms. Further studies found that µ-receptors are located throughout the brain, especially in the cerebral cortex, striatum, hippocampus, locus coeruleus, and dorsal horn of the spinal cord (Arvidsson et al., 1995).
Although this is a fair overview of the neural mechanisms of pleasure and pain perception, readers should be aware that there is no singular pleasure or pain “center,” but rather a pain “system” projecting to network of somatosensory (S1, S2, insular cortex IC, limbic (IC, anterior cingulate cortex), and associative (PFC) structures (Apkarian, 2005).
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