Table 1.

Research methodologies and example results in the neuroimaging of pain

Pain induction method	Within‐subject comparisons	Between‐subject/group comparisons	Mixed comparisons
1. Experimental pain induction	Modulation of pain processing by: Cognitive distraction (e.g. Bantick et al., 2002) Expectation (e.g. Lorenz et al., 2005; Brown et al., 2008a; Atlas et al., 2010) Hypnotic analgesia (e.g. Rainville et al., 1999; Huber et al., 2013) Placebo treatments (e.g. Wager et al., 2004; Watson et al., 2009) Mindfulness meditation (e.g. Brown and Jones, 2010; Zeidan et al., 2011) Endogenous opioid function (Zubieta et al., 2001; Sprenger et al., 2006)	Cerebral pain processing affected by individual differences in pain catastrophising (e.g. Gracely et al., 2004; Michael and Burns, 2004; Brown et al., 2014; Loggia et al., 2015), fear and anxiety (e.g. Ochsner et al., 2006) and altered sleep (Petrov et al., 2015).	Studies are needed to investigate the moderator effects of between‐subjects characteristics (e.g. pain catastrophising) on within‐subject contextual modulation of pain (e.g. attention, expectation and placebo effects).
2. Chronic pain presence/absence or induction/suppression	Reductions opioid receptor binding within the medial pain system in patients with post‐stroke pain (Jones et al., 1999) and arthritic pain (Jones et al., 1994). Fluctuations in chronic low back pain correlating with functional connectivity of medial prefrontal cortex with other brain regions (Baliki et al., 2011).	Reduced opioid receptor binding in fibromyalgia versus controls (Harris et al., 2007), post‐stroke pain versus controls (Willoch et al., 2004) and central versus peripheral neuropathic pain (Maarrawi et al., 2007). Changes in resting‐state functional networks between chronic pain conditions and controls (Baliki et al., 2014; Kucyi et al., 2014; Fallon et al., 2016)	Future research could investigate (i) interactions between psychological factors (e.g. pain catastrophising) and changes in opioid receptor binding in response to chronic pain and (ii) how patients with different patterns of network connectivity in the brain differ in endogenous opioid system functioning.
3. Chronic pain versus acute pain	Greater processing in the medial pain system for chronic arthritic than for acute pain (Kulkarni et al., 2007; Parks et al., 2011).	N/A – requires within‐subject comparisons	Future studies could investigate whether differential medial pain system activity in chronic versus acute pain is related to levels of psychological distress.
4. Chronic pain natural history or treatment response	Structural brain changes from of arthroplasty in osteoarthritis (Gwilym et al., 2010). Differences in brain function and structure bertween subacute and chronic pain stages of low back pain (e.g. Baliki et al., 2012). Changes in somatosensory cortical reorganization with recovery in patients with Complex Regional Pain Syndrome (Maihöfner et al., 2004). Changes in prefrontal cortex structure or function with cognitive‐behavioural therapy (e.g. Seminowicz et al., 2013; Čeko et al., 2015) or mindfulness meditation (e.g. Brown and Jones, 2013).	N/A – requires within‐subject comparisons	Identifying patient subgroups with different prospective outcomes from baseline brain structure/function (Baliki et al., 2012). Studies are required to identify predictors of response to difference treatments, such as cognitive‐behavioural therapy, analgesics, physical therapies.

Studies can be broadly categorised into (i) those that use a standardized acute or tonic pain stimulus to understand different aspects of pain processing, (ii) studies where patients are scanned in different clinical pain states, (iii) where responses are compared between standardized experimental pain and clinical pain, (iv) longitudinal observations of changes in pain processing according to naturalistic changes or treatment‐related changes. Furthermore, in each case, studies can make within‐subject, between subject or mixed comparisons. Examples are provided of studies within each category where possible. Studies further down and/or to the right side of the table generally require greater sophistication and resources, and are therefore less common, but provide greater mechanistic insights into chronic pain vulnerability.