New Study Advances Understanding of How Heat and Pain Are Sensed and How Touch Can Become Painful

A study by investigators from the National Center for Complementary and Integrative Health and the National Institute of Dental and Craniofacial Research provides new insights into how the nervous system detects heat and touch and how inflammation modifies these processes to trigger pain. This research was conducted and supported by the National Institutes of Health (NIH) intramural research program and published in the journal Nature.

Nerve terminals in the skin allow us to make fine distinctions about our surroundings. However, after injury or inflammation, it has long been believed that these neurons must respond differently than they normally do since they now trigger pain. In fact, three types of inflammatory pain are clinically recognized: ongoing pain, heightened pain (hyperalgesia), and pain from normally innocuous stimuli (allodynia).

During the past 30 years, researchers have been developing an understanding of the mechanisms by which somatosensory neurons detect touch and temperature. This new study redefines current models of sensory discrimination at the cellular and molecular levels. The investigators used a combination of techniques—functional imaging and multiplexed in situ hybridization—to reveal how different classes of somatosensory neurons in mice respond to heat and mechanical (touch) stimuli and how this representation is transformed by inflammation to cause ongoing pain, thermal hyperalgesia, and tactile allodynia.

In a key set of experiments, injection of prostaglandin E2 (a signaling molecule that induces inflammation and pain) led to long-lasting activity and sensitization to heat in particular groups of nociceptors (sensory neurons that respond to potentially harmful stimuli). The protein TRPV1 (the receptor for the spicy component of chili peppers) is present in these neurons and is needed to sensitize them to heat. Tactile allodynia in response to inflammation worked in a different and quite unexpected way; it was not caused by changes in touch detection. Instead, ongoing firing of nociceptors was necessary to make gentle touches painful; tactile allodynia did not occur when the functioning of these neurons was blocked. This finding is consistent with previous research at NIH showing that the ion channel PIEZO2 plays a crucial role in this type of pain. 

These results enhance the understanding of how touch and temperature are detected at the cellular and molecular levels and provide new insights into how inflammation reshapes responses to cause pain. The findings of this study may be helpful in developing effective treatments for specific types of pain.