Pain and Blood Pressure

Thomas G. Pickering, MD, DPhil

In This Article

Altered Pain Perception in Hypertensive Subjects -- Findings That May Have Practical Implications

A very consistent finding in studies of pain perception in hypertensive subjects has been that they do not feel pain as intensely as normotensives.[5,6,7] This has also been demonstrated in a variety of animal models of experimental hypertension. In the Goldblatt hypertension model, clipping a renal artery of a rat induced hypalgesia as well as hypertension.[8] The same phenomenon has been reported in other models like DOCA-salt hypertension Dahl salt-sensitive rats on a high-salt diet, and spontaneously hypertensive rats.[7] These suggest hypalgesia is merely a consequence of the hypertension, but this is not necessarily the case. It is possible to breed strains of rats where the diminished pain sensitivity does not cosegregate with the hypertension, and lowering the blood pressure with antihypertensive drugs does not necessarily reverse the hypalgesia.[7] Although clipping the renal artery raises the blood pressure in all strains of rats, the hypalgesia does not occur in all strains.[8] There is also a chicken-and-egg question because in spontaneously hypertensive rats the hypalgesia is present at a young age, even before the hypertension develops.[9]

Human studies have used a number of different painful stimuli, such as tooth pulp, electrical stimulation, and thermal stimulation.[6] One of the interesting findings is that the association between pain sensitivity and blood pressure holds even within the normal range of blood pressure.[7] There is also evidence that hypalgesia may precede hypertension because there is a series of observations that normotensive persons with a family history of hypertension show hypalgesia,[10] and more convincingly by a recent finding that pain tolerance measured at age 14 years predicts ambulatory blood pressure at age 22 years.[11]

It is clear that there is a close but not invariable relationship between pain sensitivity and blood pressure, which raises the next question: What is the mechanism? It has been known for many years that stimulation of baroreceptors lowers cerebral arousal. Some years ago I was involved in a study designed to test the hypothesis that raising the blood pressure in rats would reduce the effects of a painful stimulus as a result of this baroreflex effect.[12] Rats were put on a treadmill and exposed to a painful electrical stimulus (stimulation of the trigeminal nucleus). They were trained so that if they started to run they could avoid the stimulus. When blood pressure was raised by infusing phenylephrine, this response was attenuated, as shown by less running on the treadmill. To show that this was mediated by the baroreceptors, another group of rats that had their baroreceptors denervated was put through the same procedure, but in this instance raising the pressure with phenylephrine did not affect their running. This experiment had two important implications: first, stimulation of the baroreceptors might be one explanation for the hypalgesia of hypertension, and second, even more interestingly, hypertension could be a learned behavior pattern that would reduce the effects of stress.

Support for the involvement of the baroreceptors comes from human studies where baroreceptor stimulation using neck chamber suction and pressure has been found to modulate pain sensitivity.[13] Whereas this might explain some of the acute effects, it is less easy to explain the chronic relationship between hypalgesia and hypertension because the baroreceptors would be expected to reset to the higher level of pressure. It must be admitted that the baroreceptor analgesic effects do not necessarily reset in parallel with the blood pressure effects, and in fact denervation of the baroreceptors reverses the hypalgesia in rats with chronic experimental hypertension.[14]

The proposed baroreceptor mechanism has basically a peripheral origin because it depends on the inhibitory effects of baroreceptor stimulation by increased blood pressure. Another possibility is that the hypalgesia-hypertension relationship depends on a central link between the regulation of pain and of blood pressure. The central nervous system pathways for pain are complex and diffuse, but some areas, such as the nucleus tractus solitarius (the first relay point of the baroreceptor afferents in the brain), the periaqueductal gray matter, and the locus ceruleus appear to be involved in the regulation of both pain and blood pressure.[7] A promising area of research is the role of endorphins, which are thought to be the most important neurotransmitters for pain perception. In rats, hypertension-associated hypalgesia can be suppressed by the opiate antagonist naloxone.[9] Furthermore, elevated levels of endogenous opioids have been found in the brains of rats in several models of experimental hypertension, including spontaneously hypertensive rats and Goldblatt hypertensive rats.[15] In a human study comparing normotensive individuals with borderline hypertensives, Schobel et al.[15] found that administering a painful stimulus (pinching the skin) resulted in an increase of MSNA, plasma norepinephrine, and blood pressure. Opioid blockade with naloxone increased the subjective pain rating and the MSNA response in the normotensives but did not affect either in the hypertensives. The authors concluded that these results did not support the idea that the reduced pain sensitivity in the hypertensives (which they did observe in this sample) could be explained by increased activity of the endogenous opioid system.


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