Study Elucidates Link Between Primary and Referred Pain

Although the association between primary and referred pain is generally not well characterized, a study by an Iowa research team has shed more light on the link between the two pain types. The investigators found that a threshold level of primary pain is necessary to induce referred pain, and that there is a progressive relationship between referred pain and the intensity of primary pain.

“We still don’t know that much about referred pain,” said Laura Frey-Law, MS, MPT, PhD, associate professor of physical therapy and rehabilitation science at the University of Iowa, in Iowa City. “One proposed theory is well documented and suggests that to get referred pain, one needs to hit a threshold level of local or primary pain. So we decided to look at that more closely.”

To that end, Dr. Frey-Law and her colleagues enrolled 91 healthy adults (48 women) into the investigation; each was between the ages of 18 and 48 years. Each patient received four different infusions to the anterior tibialis muscle over five minutes: 40 mL per hour isotonic saline, 80 mL per hour isotonic saline, 40 mL per hour 5.2 acidic phosphate buffer and 80 mL per hour acidic phosphate buffer. Patients were blinded to the study solution; infusions came in two visits spaced approximately one week apart.

Patients were asked to verbally rate their pain every 30 seconds during the infusion using the Borg Category Ratio (CR10) scale at both the infusion site (which represents primary pain) and at the ankle/foot, a well-established site for referred pain. “The saline induces a little bit of pain, and is usually from distention,” Dr. Frey-Law said in an interview. “The acid, on the other hand, induces a deep ache, kind of like a muscle cramp.”

As reported primary pain intensity was lowest with the slower saline infusion (1.3), followed by the faster saline infusion (1.6), the slower acid infusion (2.1) and the faster acid infusion (3). The incidence of referred pain followed the same progression, affecting 36.3%, 44%, 64.8% and 75.8% of patients, respectively.

Logistic regression revealed that the odds of having referred pain rose 50% for each unit’s increase in primary pain intensity ratings. The predictability of referred pain incidence is optimal when primary pain intensity was approximately 2.5 to 3 on the CR10 scale.

“There was also a bit of a jump [in pain intensity] between the saline and the acid,” Dr. Frey-Law said. “So although the intensity of the pain was important, the source of the pain also seems to be important. The fact that the type of infusion becomes almost as much of a predictor as the pain intensity itself suggests that not all primary pain will equally induce referred pain,” she said.

These findings suggest that by treating primary pain, practitioners may be treating the referred pain as well.

Marie H. Bement, MPT, PhD, associate professor of physical therapy at Marquette University in Milwaukee, noted that the study highlights the importance of managing primary pain. “If primary pain is not well managed, it could progress to referred pain or even widespread pain, which is the hallmark of central sensitization,” she said. “To me, this study indicates that you need good primary pain management as a way to treat—or pre-empt—referred pain. It really highlights the importance of management and prevention.”