Classical Conditioning Fails to Elicit Allodynia in an Experimental Study with Healthy Humans
One page on PainSci cites Madden 2017: Chronic Pain as a Conditioned Response
PainSci commentary on Madden 2017: ?This page is one of thousands in the PainScience.com bibliography. It is not a general article: it is focused on a single scientific paper, and it may provide only just enough context for the summary to make sense. Links to other papers and more general information are provided wherever possible.
This was a rare direct test of whether classical conditioning could induce pain from non-painful stimuli in humans, via the mechanism of classical conditioning. How exactly does one attempt that?
Madden et al. exposed 34 participants to simultaneous non-painful vibration and painful heat. They were trying to “teach” the subjects' nervous systems that vibration equals pain through repeated exposure. Then they checked to see if their pain thresholds had in fact been reduced for the conditioned stimulus, by applying vibration alone.
It did not work: there was no statistically significant reduction in pain thresholds. On the contrary, they actually went up! A habituation effect, probably (see May et al) — the actual opposite of being conditioned to feel more pain when vibrated, these subjects were “conditioned” to feel less pain. That effect is worth understanding, regardless of the implications for conditioning of pain, but it’s certainly a blow against
Importantly, there was no effect from factors like gender, pain catastrophizing, and a lousy mood (“negative affect,” prone to fear, sadness, anxiety).
Why more study really is needed in this case
The study concludes that classical conditioning definitely did not induce allodynia under these conditions, but also makes it clear that “this is isn’t over”:
Importantly, this study does not provide conclusive evidence that allodynia cannot be induced using classical conditioning — only that the present carefully designed paradigm did not induce allodynia in this sample. It remains possible that allodynia might be induced under different conditions — perhaps with different stimuli, different anatomical sites, or different conditions of implicit threats.
Indeed, all the key limitations of this study cast a bit more doubt on whether the conditions of the trial could possibly be fertile ground for growing a crop of conditioned pain:
- Timing! The “simultaneous” pairing of stimuli was not perfectly aligned, so maybe the conditioning wasn’t good enough.
- Vibration? Visual and auditory stimuli might have worked better (as used in other studies).
- Masking! While participants were blinded — an important feature of any trial — being unaware of the pairing might have sabotaged the conditioning a bit. (But is awareness required for classical conditioning in this context? Unknown!)
original abstract †Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.
OBJECTIVE: Associative learning has been proposed as a mechanism behind the persistence of pain after tissue healing. The simultaneous occurrence of nociceptive and non-nociceptive input during acute injury mimics the pairings thought to drive classical conditioning effects. However, empirical evidence for classically conditioned allodynia is lacking. We aimed to manipulate pain thresholds with a classical conditioning procedure that used non-nociceptive somatosensory stimuli as conditioned stimuli (CS) and nociceptive stimuli as unconditioned stimuli. We also explored the influence of gender, depression, anxiety, negative affect, and pain catastrophizing on the main manipulation.
DESIGN: Thirty-four healthy humans participated in a differential classical conditioning procedure that used vibrotactile stimulations at two different locations as CS. In an acquisition phase, CS+ was paired with painful thermal stimulation, and CS- with nonpainful thermal stimulation. Heat pain threshold was assessed during paired heat-CS trials before and after acquisition. A 2 (time: 1 and 2) x 2 (condition: CS+ and CS-) repeated-measures analysis of variance compared pain thresholds before and after acquisition. Exploratory analyses explored the influence of gender, depression, anxiety, negative affect, and pain catastrophizing. Postexperiment questions investigated participants' awareness of the contingencies employed.
RESULTS: The classical conditioning procedure did not alter pain thresholds. Exploratory analyses did not reveal any influence of individual differences. Thirty of the 34 participants were unaware of the contingencies between stimuli.
CONCLUSIONS: The results of this study provide no evidence that allodynia can be induced in healthy humans using a classical conditioning procedure with simultaneous timing.
related content
- “Within-session sensitization and between-session habituation: a robust physiological response to repetitive painful heat stimulation,” May et al, European Journal of Pain, 2012.
- “In search of conditioned pain: an experimental analysis,” Kang et al, Pain, 2023.
- “Do clinicians think that pain can be a classically conditioned response to a non-noxious stimulus?,” Madden et al, Manual Therapy, 2016.
- “Can Pain or Hyperalgesia Be a Classically Conditioned Response in Humans? A Systematic Review and Meta-Analysis,” Madden et al, Pain Med, 2016.
This page is part of the PainScience BIBLIOGRAPHY, which contains plain language summaries of thousands of scientific papers & others sources. It’s like a highly specialized blog. A few highlights:
- Restoring trust in menopause management: menopause hormone therapy is not a panacea, and physical activity remains a critical intervention. Tulloh 2025 Br J Sports Med.
- Common interventional procedures for chronic non-cancer spine pain: a systematic review and network meta-analysis of randomised trials. Wang 2025 BMJ.
- Gabapentinoids and Risk of Hip Fracture. Leung 2024 JAMA Netw Open.
- Classical Conditioning Fails to Elicit Allodynia in an Experimental Study with Healthy Humans. Madden 2017 Pain Med.
- Topical glyceryl trinitrate (GTN) and eccentric exercises in the treatment of mid-portion achilles tendinopathy (the NEAT trial): a randomised double-blind placebo-controlled trial. Kirwan 2024 Br J Sports Med.