Current understanding of the mixed pain concept: a brief narrative review

Figures & data

Figure 1. The three different types of pain defined by the IASP give rise to overlap which can be acknowledged as “mixed pain” (Freynhagen©). Conditions described as “mixed pain” in the literature share a common characterization of manifesting clinically with a substantial overlap of the different known pain types.

Table 1. Mixed pain: practice pearls.

• Currently, the diagnosis of mixed pain is made based on clinical judgement following detailed history-taking and thorough physical examination, rather than by formal confirmation following explicit screening or diagnostic criteria (which are, as yet, not available).  • When encountering a patient who presents with an overlap of nociceptive and neuropathic symptoms, consider mixed pain as a working diagnosis.  • For a patient with a working diagnosis of mixed pain, consider early treatment with a combination of agents targeting nociceptive and neuropathic mechanisms.  • For a patient with a working diagnosis of mixed pain, perform a thorough evaluation for comorbidities (e.g. disturbed sleep, depression, anxiety) and manage accordingly.

Table 2. Important questions for future research.

• How are “peripheral sensitization” and “central sensitization” detected and quantified?  • What are the underlying mechanisms of mixed pain?   ^ Is mixed pain the manifestation of neuropathic and nociceptive mechanisms operating simultaneously or concurrently?   ^ Or is it the result of an entirely independent pathophysiological mechanism – distinct from nociceptive, nociplastic and neuropathic pain?  • Is mixed pain more frequent when pain occurs in large areas of the body?  • Is an independent category of “mixed pain” in the pathophysiological classification of pain justified?  • Which (chronic) pain states can be classified as mixed pain?  • Why do patients with mixed pain exhibit more comorbidities?  • Why is mixed pain specifically associated with lower physical and mental quality of life?  • What screening and/or diagnostic tools can be utilized to identify mixed pain?  • What therapeutic strategies/agents can be used to target potentially distinct mixed-pain mechanisms?