Designing Out Pain
2012-10-01 0:00

By Greg Mayhall, MD, and Rodney E. Shackelford, DO, Ph.D. |

Our present understanding of the neuromolecular biology underlying pain perception should allow several aspects of pain treatment to be radically improved in the near future. For example, better analgesics could be created based on an improved understanding of how pain perception arises and how it travels within the nervous system. The genetic variations underlying pain perception can be genetically analyzed and applied directly to patient care.

Instead of an analgesic “hit and miss” approach, molecular analysis of the variants in an individual’s pain-associated genes would allow for a far more accurate assessment of the treatments needed to safe and effective pain treatment (i.e., “pain genotyping”). The technology to do this already exists and is commonly applied in other molecular pathologic tests.

Since the neuromolecular biology underlying pain perception appears to be highly conserved in all vertebrates, the study of pain perception-associated gene activities sheds light on animal pain perception. The present data strongly supports that animals perceive pain as well, or nearly as well as do humans. This data has important implications for how we treat animals.

It might be possible to alter the human genome to eliminate or reduce pain signals, to help individuals with chronic pain syndromes, or those who literally have a painful genetic inheritance, without the need of constant and sometimes dangerous pharmacologic interventions. Researchers at the University of Pittsburgh have demonstrated a gene therapy for neuropathic pain in an animal model as one example.
As the philosopher David Pearce has suggested, should the human race one day begin to ‘write its own genome”, then the genes regulating pain perception could be altered to allow a lessening of the miserable, often horrendous aspects of pain perception, while still maintaining its usefulness in avoiding physical damage. We could simply design pain out of the human experience.

Pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage1” Physical pain perception (nociception) is adaptive and protects complex organisms from tissue damage while inducing tissue protective and healing promoting behaviors.

Pain responses are found in all complex organisms, including fish, amphibians, reptiles, birds, and mammals. Although conscious pain perception cannot currently be measured in animals, adverse behavioral changes following painful events (reduced with analgesia), demonstrate that animals almost certainly perceive pain. Additionally, as pain perception is mediated by neocortical function (found in all vertebrates), and pain-inducing stimuli elicits very similar global vertebrate brain gene expression pattern changes, there is little reason based on behavioral, neuroanatomic, or molecular studies to doubt that most animals experience pain – for mammals, probably very similar to human pain perception.

Medically, untreated pain is a major problem in the US, with 50% of hospitalized patients being undertreated for pain, and 56% and 82% of individuals with cancer and HIV being similarly undertreated, respectively. See for example

However, over the past ten years, our understanding of the genetics underlying pain perception has vastly increased. Presently some three hundred-gene products have been identified which either modulate, or cause severe gains or losses in pain perception abilities. Based on identical human twin studies with comparison to data from mice, there are about twenty-four genes that carry common variations that significantly contribute to pain perception.


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