Hyperalgesia

Original Editor - Melissa Coetsee

Top Contributors - Melissa Coetsee, Kim Jackson, Vidya Acharya and Carina Therese Magtibay  

Introduction

IASP definition:

"Increased pain from a stimulus that normally provokes pain."

Hyperalgesia is a clinical term used to described the phenomenon of an increased pain response to a painful stimuli (such as pin prick, deep pressure, extreme heat/cold). It does not imply a single pain mechanism, but is associated with peripheral sensitisation and central sensitisation.

Hyperalgesia is normal protective response after tissue damage and will usually subside as healing occurs. It may however increase over time in certain conditions, such as neuropathic pain conditions, and may be present in the absence of tissue injury.

Aetiology/Mechanism

Hyperalgesia may involve a reduction in nociceptive firing threshold, and an increase in the supra-threshold response.The end result is amplified nociception and an increase in pain intensity.

• Primary Hyperalgesia: Hyperalgesia that occurs at the site of injury and is often a reflection of peripheral sensitisation. It occurs as a result of reduced activation threshold and increased responsiveness of nociceptors (A-delta and C-fibres).
• Secondary Hyperalgesia: Hyperalgesia in an area adjacent to or remote from the site of injury.It is maintained by changes in the central processing of sensory information, including sensitisation of the spinal nociceptive neurons and altered descending inhibition.Secondary hyperalgesia reflects that central sensitisation (at spinal cord/brain level) is at play. It involves sensitisation of second-order neurons in the dorsal horn, as well as activation of nociceptive neurons in the brainstem and thalamus.

It is important to remember, that in acute injuries, the finding of hyperalgesia is a normal adaptive response. Since the injured tissue is vulnerable, the nociceptive system adapts by becoming sensitised to ensure tissue protection.In such a case hyperalgesia would be an appropriate shift in pain threshold. It is however possible for this normal response to be exaggerated and does not always reflect the severity of an injury.

If hyperalgesia does however occur long after tissue healing has occurred or in the absence of damaged tissue, it is considered maladaptive and may indicate nerve damage, ongoing nociception and/or sensitisation and can contribute to chronic pain states. Persistent tissue injury and inflammation can also result in ongoing hyperalgesia.

Nerve Sensitisation

As mentioned above, hyperalgesia occurs as a result of nociceptive sensitisation. The following mechanisms cause nerve sensitisation:

• Neurogenic Inflammation: Peripheral nociceptors participate in the inflammatory process by releasing neuropeptides (like Substance P)
• Inflammatory mediators (histamine, prostaglandin, bradykinin, cytokines)
• Glial cells can release proinflammatory cytokines
• Change in pH associated with inflammation

Risk Factors

The following factors may increase the risk of maladaptive hyperalgesia:

• Chronic Inflammation: Excess fat results in chronic release of inflammatory mediators which could increase nociceptive sensitisation
• Immune response: When an injury occurs while the immune system is active (eg. fighting an acquired infection), exaggerated hyperalgesia is more likely since nociceptors are already sensitised
• Stress: Pain pathways are modulated by stress, and exposure to chronic stress can produce maladaptive changes in pain processing leading to stress-induced hyperalgesia.
• Opioid use: Opioid-induced hyperalgesia occurs when opioids paradoxically enhance pain. This can occur with acute or chronic exposure to opioids. Opioid tolerance and withdrawal can also affect pain sensitivity as it affects descending pain modulation.

Conditions

Listed below are some conditions that may present with ongoing hyperalgesia:

• Neuropathic Pain: primary and secondary hyperalgesia
• Postherpetic Neuralgia: primary hyperalgesia
• Neuropathies
• Polyneuropathy such as HIV-related Neuropathy and Diabetic Neuropathy
• Brachial Plexus Injury
• Fibromyalgia
• Irritable Bowel Syndrome
• Chemotherapy induced peripheral neuropathy
• Central Sensitisation
• Peripheral Sensitisation
• Complex Regional Pain Syndrome (CRPS)
• Chronic Low Back Pain
• Osteoarthritis
• Rheumatoid Arthritis
• Post-amputation stump pain
• Central nervous system disorders: Post-stroke pain, Multiple Sclerosis, Spinal Cord Injury

Differential Diagnosis

Hyperalgesia vs Allodynia

Another clinical term that needs to be differentiated from hyperalgesia, is allodynia. Where hyperalgesia refers to changes in the intensity of the sensation of pain, allodynia refers to changes in the quality of sensation.

Allodynia occurs when non-nociceptive afferents become sensitised, which results in non-painful stimuli becoming painful. Hyperalgesia involves sensitisation of nociceptors altering the intensity of pain for given painful stimulus.

Although allodynia and hyperalgesia are distinct clinical terms, they can and often do co-exist.

Assessment

• Hyperalgesia to various painful stimuli can be assessed, and forms part of Quantitative Sensory Testing (QST). QST is a way to evaluate the excitability of different pain pathways and can provide valuable insight into pain mechanisms.

• Always compare to the unaffected side or a body site distant from the affected area (especially if there is bilateral involvement)
• Mental health screening for depression and/or anxiety
• History of chronic medication and other conditions which could contribute to hyperalgesia (eg. neuropathies, diabetes, HIV, chemotherapy, stroke)
• Full neurological examination to assess for nerve damage and neuropathic pain (including sensation, reflexes and muscle power).

Treatment

Acute injuries

• The focus is to minimise the development of sustained/chronic hyperalgesia. Pain needs to be addressed early to prevent ongoing nociception
• Control excessive inflammation with rest, anti-inflammatories and ice
• It may be necessary to temporarily immobilise/brace the affected joint and adjust weight bearing status to ensure minimal ongoing nociception
• Once inflammation has settled, fear of movement needs to be addressed/prevented by encouraging and guiding graded movement and loading
• Psychologically informed communication is very important. Instilling unnecessary fear and negative expectations by using negative language (eg. "your ankle is pretty messed up" or "this is the worst sprain I've seen") can actually have a nocebo effect and negatively influence descending inhibition. Realistic caution and prognosis should be shared using safe and non-threatening language.
• Address false beliefs and help the patient to process any fears related to the injury
• See the PEACE and LOVE acute injury protocol

Chronic pain

• See the page on Neuropathic pain and Neuropathic medication for hyperalgesia related to nerve lesions.
• Avoid negative language in chronic conditions (eg. "bone on bone", "degenerative") to minimise the nocebo effect.
• Use positive communication strategies to address false beliefs and fears. These include motivational interviewing, positive framing, empathetic communication.
• Pain Neuroscience Education (PNE)
• Psychosocial interventions: Counselling may be recommended if signs of depression are detected. Biofeedback, mindfulness training, and cognitive behavioural therapy can influence descending inhibition and therefore alter pain perception.
• Graded Motor Imagery - especially in CRPS
• Ice and NSAIDs can be effective in controlling chronic or neurogenic inflammation
• Transcutaneous Electrical Nerve Stimulation (TENS) may reduce chronic inflammatory hyperalgesia. It may be necessary to apply TENS on areas remote from the painful area if the painful area is to sensitive.
• Graded exposure to movement: Avoid "pushing through" the pain, and encourage pacing and gradually increase loading

Conclusion

Hyperalgesia is a phenomenon that is continually being researched and interpretation of this clinical sign may change as research evolves. It is important to assess hyperalgesia early on and careful assessment of various biological and psychological mechanisms are required to ensure targeted treatment strategies. Hyperalgesia is normal in acute injuries, but also plays a role in the development of chronic pain states.