A Latin American consensus meeting on the essentials of mixed pain

Figures & data

Table 1. Initially planned topics for the consensus meeting.

1. What is mixed pain?

Does it have its own pathophysiological entity or is it a temporary summation of pain types and phenomena? b.   Is the nociplastic component constant or occasional? c.   Is it nociplastic or dysfunctional? d.   Pathological entities that can be included in mixed pain.

2. The value of clinical symptoms in the diagnosis of mixed pain.

Anamnesis Self-administered questionnaires

3. The value of the examination in the diagnosis of mixed pain.

Facial expression examination Physical examination (Quantitative Sensory Testing) Neurophysiological examination

4. The value of functional MRI in the diagnosis of mixed pain.

Anatomical Neurovascular Neurochemical

5. Non-opioid analgesics, NSAIDs, and opioids in the treatment of mixed pain (Which ones to use? When to use them? For how long?).

Non-opioid analgesics NSAIDs Opioids

6. Neuromodulators in the treatment of mixed pain (Which ones to use? When to use them? For how long?).

Antidepressants Anticonvulsants Others

7. The role of B vitamins in the treatment of mixed pain

Monotherapy Combined therapy with NSAIDs Combination therapy with opioids Combined therapy with anticonvulsants

8. Cognitive-behavioral therapy in the treatment of mixed pain

Guided imagery - virtual reality Systematic desensitization Reframing - reprogramming Meditation

Figure 1. Flow chart of the literature review process.

Figure 2. Results of statistical evaluation of the topic “What is mixed pain?”.

Table 2. Pathologies where mixed pain can be expressed.

Conditions where mixed pain can be expressed

Different osteoarthrosis: knee, hip, spine

Chronic low back pain and chronic neck pain

Chronic postoperative pain

Chronic posttraumatic pain

Immune-mediated joint pain (Lupus, rheumatoid arthritis, scleroderma, Raynaud’s)

Complex regional pain syndrome

Chronic neurological problems (Stroke, Parkinson’s disease)

Amputee pain (phantom limb) (No/yes stump neuromas)

Fibromyalgia

Chronic abdominal and pelvic pain

Myofascial syndrome

Orofacial pain

Oncologic pain

Cancer survivor

Figure 3. Results of statistical evaluation of the topic “Diagnosis of mixed pain”.

Figure 4. Results of statistical evaluation of the topic “Value of physical examination for the diagnosis of mixed pain”.

Figure 5. Results of statistical evaluation of the topic “Value of functional magnetic resonance imaging (fMRI) in the diagnosis of mixed pain”.

Figure 6. Results of statistical evaluation of the topic “Non-opioids analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids in the treatment of mixed pain”.

Figure 7. Treatment suggestion for patients with mixed pain – an escalation ladder.

Figure 8. Results of statistical evaluation of the topic “Neuromodulators in the treatment of mixed pain”.

Figure 9. Results of statistical evaluation of the topic “The role of B vitamins in the treatment of mixed pain”.

Figure 10. Results of statistical evaluation of the topic “Cognitive behavioral therapy in the treatment of mixed pain”.

Table 3. Overview of recommendations and key messages agreed on by the consensus committee.

What is mixed pain?

Q1A - Definition of mixed pain: “Dolor mixto es una condición compleja en la que se suman componentes de dolor nociceptivo, neuropático y nociplástico” Mixed pain is a complex condition including components of nociceptive, neuropathic, and nociplastic pain.

Q1B - Physiopathology of mixed pain: Mixed pain may include different pathological entities, each with its own mechanism and manifestation at different time points in the clinical course

Q1C - Pathologies of mixed pain include:

Different osteoarthrosis: knee, hip, spine Chronic low back pain and chronic neck pain Chronic postoperative pain Chronic posttraumatic pain Immune-mediated joint pain (Lupus, rheumatoid arthritis, scleroderma, Raynaud’s) Complex regional pain syndrome Chronic neurological problems (Post-cerebrovascular accident, Parkinson’s) Amputee pain (phantom limb) (No/yes stump neuromas) Fibromyalgia Chronic abdominal and pelvic pain Myofascial syndrome Orofacial pain Oncologic pain Pain of cancer survivor

Diagnosis of mixed pain:

Q2A - Rule out the possibility of mixed pain, whenever a patient presents with neuropathic pain.

Q2B - Routinely use of the questionnaire by McGill as an approximation for mixed pain.

Q2C - The use of validated questionnaires (DN4, LANSS, CSI) that evaluate specific situations is recommended.

Q2D - Outlook: Conduct a multicenter study in Latin America to describe mixed pain conditions through the McGill pain questionnaire.

Value of physical examination for the diagnosis of mixed pain: Q3A - Assessment of facial expressions for the evaluation of pain in the vulnerable population is recommended.

Q3B - Bring the study of facial expression into clinical practice.

Q3C - In the physical examination, the presence of pain of high intensity with more than one component at the same time is very important for its prognosis.

Q3D – The use of QST to assess mixed pain is not recommended, due to its very low evidence.

Value of functional magnetic resonance imaging (fMRI) in the diagnosis of mixed pain:

Q4A - It is currently not possible to draw conclusions from the existing literature or to make well-founded recommendations on the benefit of magnetic resonance imaging (MRI) in mixed pain diagnosis.

The correlation between clinical and radiological findings in the different entities and painful states must be validated.

Non-opioid analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids in the treatment of mixed pain:

Q5A - For the use of opioids, it was discussed to refer to a Cochrane review about long-term management of chronic noncancer pain (Noble et al. 2010)

Q5B - Outlook: To individually review mixed pain syndromes and to establish the levels of evidence for the used drugs in their management in the future.

Q5C - Use existing pain prescription guidelines for the time being.

Q5D - Extrapolate the indications of different drugs for mixed pain.

Neuromodulators in the treatment of mixed pain:

Q6A - Refer to the diagram about treatment proposals for patients with mixed pain presented herein.

Q6B - Outlook: add a Venn diagram including pathologies and treatments to the new presented diagram in the future.

Q6C - Suggestion to use the Cochrane review by Wiffen et al. 2010 about the use of anticonvulsant drugs as a basis.

The role of B vitamins in the treatment of mixed pain:

Q7A - The use of vitamin B12 as a monotherapy for the management of low back pain is recommended.

Q7B - The use of vitamins B1, B6, and B12 as an analgesic adjuvant combined with NSAIDs (diclofenac) is recommended.

Q7C - The use of gabapentinoids combined with vitamin B complex is recommended for treatment of diabetic neuropathy and post-surgical pain.

Cognitive behavioral therapy in the treatment of mixed pain:

Q8A - Meditation, virtual reality, and psychological support significantly improve chronic pain. Some studies may suggest their use in acute pain.

Q8B - Outlook: Suggestion to carry out specific studies in mixed pain in the future.

Q8C - Physical therapy should be added to pain management.