Pathophysiology of pain in postherpetic neuralgia: A clinical and neurophysiological study

Abstract

Postherpetic neuralgia is an exceptionally drug-resistant neuropathic pain. To investigate the pathophysiological mechanisms underlying postherpetic neuralgia we clinically investigated sensory disturbances, pains and itching, with an 11-point numerical rating scale in 41 patients with ophthalmic postherpetic neuralgia. In all the patients we recorded the blink reflex, mediated by non-nociceptive myelinated Abeta-fibers, and trigeminal laser evoked potentials (LEPs) related to nociceptive myelinated Adelta- and unmyelinated C-fiber activation. We also sought possible correlations between clinical sensory disturbances and neurophysiological data. Neurophysiological testing yielded significantly abnormal responses on the affected side compared with the normal side (P<0.001). The blink reflex delay correlated with the intensity of paroxysmal pain, whereas the Adelta- and C-LEP amplitude reduction correlated with the intensity of constant pain (P<0.01). Allodynia correlated with none of the neurophysiological data. Our study shows that postherpetic neuralgia impairs all sensory fiber groups. The neurophysiological-clinical correlations suggest that constant pain arises from a marked loss of nociceptive afferents, whereas paroxysmal pain is related to Abeta-fiber demyelination. These findings might be useful for a better understanding of pain mechanisms in postherpetic neuralgia.

The Role of Sensory Fiber Demography in Trigeminal and Postherpetic Neuralgias

“…However, it is important to mention the possible contributions of C-low-threshold mechanoreceptors for tactile allodynia, reported in a recent publication (Seal et al, 2009). In addition, other sensory disturbances frequently associated with PHN are paresthesia, dysesthesia, hyperalgesia, and itching (Dworkin et al, 2008;Truini et al, 2008). Many hypotheses have been proposed to explain this diversity in symptomatology during PHN.…”

“…Initially, it was proposed that there was a preferential destruction of larger myelinated fibers (Aβ fibers), leaving an excess of the small myelinated (Aδ) and unmyelinated (C) fibers interpreted as the cause of sensory dysfunction in PHN (Noordenbos, 1959;Watson et al, 1988). Recent studies have stated that all sets of sensory fibers may be affected in this condition (Truini et al, 2008;Delaney et al, 2009), and data from neurophysiological-clinical correlations suggest a relationship between constant pain and loss of Aδ and C fibers and between paroxysmal pain and Aβ fiber demyelinization (Truini et al, 2008). Furthermore, the density of epidermal innervation has been associated with the occurrence of PHN, since samples from skin biopsies, when immunolabeled with PGP 9.5 (an axonal marker), have shown a greater amount of neuritis/mm 2 in individuals without PHN than in those with PHN (Oaklander, 2001).…”

Postherpetic Neuralgia: From Preclinical Models to the Clinic

“…31,32 There is evidence that all sensory fiber types are affected in PHN, with constant pain possibly being associated with damage to nociceptive afferents and paroxysmal pain related to changes in A␤ fibers. 33 Quantitative thermal sensory testing showed greatly increased heat pain thresholds in the affected dermatome of some chronic PHN patients. 34 Thus, there is a subset of PHN patients with pain and loss of cutaneous C-nociceptor function in a region that is coextensive with allodynic skin.…”

Perception Threshold Variations of Pain Area with Herpetic Ophthalmic Neuralgia

“…Sensory disturbances and pain were carefully assessed. Before testing, all patients were interviewed and asked to indicate the severity of their current pain, to rate the pain intensity on an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain) and to describe their predominant pain in one of the following categories: constant pain, deep pain, burning pain, paroxysmal pain, lancinating pain, allodynia, paresthesia, dysesthesia, hyperalgesia, and itching [12,24].…”