Quantitative Sensory Testing (QST) - Does assessing ... - TI Pharma

1. General introduction
stimuli. C-fibres are unmyelinated and the smallest and the slowest conducting type of
primary afferents. They have the highest thresholds for activation and therefore detect
selectively nociceptive or ‘painful’ stimuli. Collectively, both Aδ- and C-fibres can be
termed as nociceptors or ‘pain fibres’, responding to noxious stimuli which may be
mechanical, thermal, or chemical (D’Mello & Dickenson 2008). However, this might
be a simplistic presumption since other authors now consider some Aβ-afferents also as
nociceptors (Djouhri & Lawson 2004). These fibres are affected in clinical pains which
may arise from different sources, for instance damage to tissue due to inflammation or
damage to nerves in case of so-called neuropathic pain (Baron 2000; 2006; Basbaum
et al 2009; Melzack et al 2001). Both may cause subsequent profound changes in the
spinal cord and the brain.
It is believed that all persistent forms of pain induce plasticity including altered
mechanisms in peripheral and central signalling, suggesting that the mechanisms
involved in pain are likely to be multiple and located at a number of sites (Dickenson
1995; Dickenson et al 2002; Schaible 2007; Treede et al 1992). In 1970, David Hubel and
Torsten Wiesel published intriguing results of plastic changes in the brain in their work
with kittens (Hubel & Wiesel 1970). In their experiments, they shut one eye by sewing
the eyelids together and electrophysiologically recorded cortical brain maps. They saw
that the portion of the kitten’s brain associated with the shut eye was not inactive, as
expected. Instead, it processed visual information from the open eye. This property
of the nervous system to adapt morphologically and functionally to external stimuli is
known as neuroplasticity.
Altered mechanisms in the peripheral and central signalling in chronic pain can lead to
hypersensitivity to peripheral stimuli. Two types of hypersensitivity can be distinguished.
First, allodynia is defined as pain in response to a non-nociceptive stimulus. In cases
of mechanical allodynia, even gentle mechanical stimuli such as a slight touch can
evoke severe pain. Second, hyperalgesia is defined as increased pain sensitivity to a
nociceptive stimulus. Here, patients experience a painful stimulus such as a prick with
greater intensity. Both, peripheral and central sensitisations are known to be involved in
the generation of hypersensitivity. Peripheral sensitisation is a reduction in threshold and
an increase in responsiveness of the peripheral ends of nociceptors. Whereas, central
sensitisation is an increase in the excitability of neurons within the central nervous
system, so that normal inputs produce abnormal responses. The increased excitability
is typically triggered by a burst of activity in nociceptors, which alter the strength
of synaptic connections between the nociceptor and the neurons of the spinal cord
(so-called activity-dependent synaptic plasticity) (Hunt & Mantyh 2001; Woolf 2010;
Woolf & Mannion 1999). As a result, an input that would normally evoke an innocuous
sensation may now produce pain (Scholz & Woolf 2002; Woolf & Salter 2000). Altered
peripheral and central signalling could be regarded as the structural correlate leading to