Applied Evidence

A new paradigm for pain?

J Fam Pract. 2016 September;65(9):598-600,602-605

From The Journal of Family Practice | 2016;65(9):598-600,602-605.

References

1. Dubner R, Gold M. The neurobiology of pain. Proc Natl Acad Sci U S A. 1999;96:7627-7630.

2. Markenson JA. Mechanisms of chronic pain. Am J Med. 1996;101:S6-S18.

3. Rainville P, Duncan GH, Price DD, et al. Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science. 1997;277:968-971.

4. Bushnell MC, Duncan GH. Sensory and affective aspects of pain perception: is medial thalamus restricted to emotional issues? Exp Brain Res. 1989;78:415-418.

5. Galer BS, Jensen MP. Development and preliminary validation of a pain measure specific to neuropathic pain: the Neuropathic Pain Scale. Neurology. 1997;48:332-338.

6. Fassoulaki A, Triga A, Melemeni A, et al. Multimodal analgesia with gabapentin and local anesthetics prevents acute and chronic pain after breast surgery for cancer. Anesth Analg. 2005;101:1427-1432.

7. Woolf CJ, Chong MS. Preemptive analgesia—treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg. 1993;77:362-379.

8. International Association for the Study of Pain Web site. IASP Taxonomy. Available at: http://www.iasp-pain.org/Taxonomy. Accessed January 10, 2016.

9. Waddell G, McCulloch JA, Kummel E, et al. Nonorganic physical signs in low-back pain. Spine. 1980;5:117-125.

10. Bushnell MC, Ceko M, Low LA. Cognitive and emotional control of pain and its disruption in chronic pain. Nat Rev Neurosci. 2013;14:502-511.

11. Villemure C, Bushnell MC. Cognitive modulation of pain: how do attention and emotion influence pain processing? Pain. 2002;95:195-199.

12. Felitti VJ, Anda RF. The relationship of adverse childhood experiences to adult medical disease, psychiatric disorders, and sexual behavior: implications for healthcare. In: Lanius R, Vermetten E, eds. The Hidden Epidemic: The Impact of Early Life Trauma on Health and Disease. Cambridge University Press; 2010. Available at: http://www.unnaturalcauses.org/assets/uploads/file/ACE%20Study-Lanius.pdf. Accessed January 11, 2016.

13. Centers for Disease Control and Prevention. Injury prevention and control: Division of violence prevention. Adverse childhood experiences. Available at: http://www.cdc.gov/violenceprevention/acestudy/. Accessed January 11, 2016.

14. Kross E, Berman MG, Mischel W, et al. Social rejection shares somatosensory representations with physical pain. Proc Natl Acad Sci. 2011;108:6270-6275.

15. Geuze E, Westenberg HGM, Jochims A, et al. Altered pain processing in veterans with posttraumatic stress disorder. Arch Gen Psychiatry. 2007;64:76-85.

16. Mickleborough MJ, Daniels JK, Coupland NJ. Effects of trauma-related cues on pain processing in posttraumatic stress disorder: an fMRI investigation. J Psychiatry Neurosci. 2011;36: 6-14.

17. Noll-Hussong M, Otti A, Laeer L, et al. Aftermath of sexual abuse history on adult patients suffering from chronic functional pain syndromes: an fMRI pilot study. J Psychoso Res. 2010; 68:483-487.

In contrast, systems plasticity (when new CNS neuronal connections are formed in response to nerve injury) takes place over the months and years following nerve injury and is often irreversible. When we recognize NPP and intervene before system neuroplastic changes occur, it may be possible to prevent pain from becoming chronic (TABLE 1⁵). In cases of nerve injury, researchers have long suspected that early and aggressive pain treatment within the first few months that may include sympathetic and peripheral neural blockade reduces the likelihood that the patient will have chronic pain.^6,7

From this discussion, one can understand why pharmacotherapeutic agents such as antiepileptic drugs and some antidepressants are effective for treating the changes in nervous system pain processing that cause NPP, and why nerve blocks and neural stimulation—treatments that alter peripheral and central pain processing—might be effective for neuropathic but not acute or chronic nociceptive pain.

It’s time to update our understanding of pain

The International Association for the Study of Pain (IASP)—a group of health care providers, scientists, and policymakers seeking to improve pain relief worldwide—notes in its definition of pain that the complaint, “I hurt” does not necessarily imply that there is a painful stimulus in the form of tissue injury.⁸ Yet most of us have been taught to think of pain solely as the result of tissue pathology, and we assume that emotional factors merely modify how the physical damage is perceived. This traditional concept of pain is incomplete. It leads clinicians to misdiagnose the cause of pain, initiate expensive and unnecessary treatment, engage in well-meaning but misguided prescribing behavior, and miss opportunities to help patients.

SIDEBAR
From periphery to brain: The process of nociceptive pain^1-4

The process by which noxious stimuli lead to the experience of sensory pain consists of 4 steps:

In transduction, nociceptors containing special molecular proteins respond to noxious modalities, such as thermal, mechanical, or chemical stimuli, and trigger nerve impulses in the nociceptive nerve fibers (nerves dedicated to pain sensation).

During transmission—the second stage of the process—information from the nociceptors in the periphery (skin, muscle, viscera) is relayed to the spinal cord mainly by 2 types of nociceptive neurons: C-fibers and A delta (Aδ) fibers. Both approach the spinal cord in a peripheral nerve and then enter the spinal cord in the dorsal root entry zone. Because Aδ fibers are thinly myelinated, they send impulses faster than unmyelinated C fibers. This is why when injury occurs, we first feel sharp, acute pain that then slowly diffuses into a duller ache.

Once the incoming signal is transmitted to the CNS at the spinal cord, primary afferent neurons synapse on second order neurons. From there, information travels on to the thalamus via multiple neurons that have the capacity to change their response patterns when activity of nociceptive fibers is sustained (as occurs in the setting of a tissue or nerve injury and perhaps in the setting of psychological trauma). This is known as modulation of the incoming nociceptive stimulus. During this step of the process, stimuli can be amplified, suppressed, or even transformed from one type to another (eg, a light touch can be modulated in such a way that it will be perceived as a burning sensation). Also, it is this step that is affected by many medications, by intrathecal drug infusions, and by spinal neurostimulators.

In perception, the thalamus then directs the pain sensation to multiple brain centers. At this step, the stimulus is finally consciously perceived as pain by the individual.

Cortical pain circuits can be activated without physical input (ie, no tissue damage, noxious stimuli, or nerve injury). This becomes important in understanding pain syndromes, such as fibromyalgia.