Table 1.

Evidence regarding biological factors involved in pain and implications for pain neuroscience education.

Biological Factor	First Author, Reference	Investigated Mechanism	Implication for Pain Neuroscience Education
(Epi)genetic	Zorina-Lichtenwalter [17]	Genetic contributions to chronic pain	Educate the patient on the role of genetic factors in the variability of stimuli responses.
	Polli [24]	Physical and psychological stressors can induce epigenetic changes in relation to chronic pain	Explain to the patient how various stressors can alter genetic expression to explain why certain stimuli can be experienced differently in other contexts.
	Nirvanie-Persaud [29]	Epigenetics play a role in the transition from acute to chronic pain	Provide understanding to the patient of how various factors, including genetic and environmental, may have led to persistent pain.
	Mauceri [30]	Epigenetic changes can facilitate peripheral and central sensitization processes	Explain to the patient how their increased sensitivity can partially be explained and maintained by changes on the genetic level.
Neural	Hasmi [35]	Shift of pain processing from nociceptive to emotional circuits with chronification of pain	Consider and discuss emotional components during the patient’s education and care, especially as pain persists.
	Bosnar Puretic [36]	Neuroplasticity can lead to central sensitization process	Educate the patient on the key concept of neuroplasticity and how the nervous system changes and sensitizes over time to help focus more on the sensitivity of the nervous system and less on damage to the tissues as pain persists.
	Catley [41]	Spinal and cortical representation changes in people with chronic pain	Educate the patient on the concept of body representation changes that can occur with chronic pain and the need for various interventions (i.e., GMI and sensory discrimination) to facilitate recovery.
	Price [53]	Linking of pain and memory mechanisms with chronic pain	Provide understanding to the patient of the concept of “pain memories” and how treatment needs to work on overcoming pain memories that might be maladaptive to function.
Endocrine	Lunde [58]	Stress response system implications within chronic pain	Educate the patient on the link between chronic pain and the stress response system to provide an understanding of the individual’s pain experience.
	Wyns [61]	Stress intolerance role in chronic pain	Explain to the patient why various stress management interventions can assist in improving chronic pain limitations.
	Haack [70]	Sleep deficiency and chronic pain alterations in endocrine function	Educate the patient on the important link between poor sleep and changes in endocrine function.
Immune	Marchand [74]	Inflammatory mediators released from immune cells contribute to persistent pain states	Educate the patient on the link between the immune system and chronic pain is critical. These facts also help explain why pain may increase or decrease based on immune system response and may not be due to tissue changes.
	Totsch [76]	Diet can influence pain through the immune system	Include education on why diet changes in a multimodal treatment could be beneficial.
	Besedovsky [77]	Sleep can influence pain through the immune system	Educate the patient on improving sleep hygiene as part of the multimodal treatment.