Table 4 Methods of experimentally inducing secondary hyperalgesia possibly involving LTP in human volunteers

Electrical nerve stimulation: C-fibres

HFS

100 Hz for 1 sec (pulse width, 2 ms), repeated five times at 10 sec intervals

Stimulation protocol and stimulated fibre type equivalent to rodent HFS paradigms inducing LTP

[19, 25, 173–175]

Ongoing IFS

intracutaneous continuous electrical skin stimulation at 5 HZ (pulse width, 0.5 ms)

[176, 188, 189, 227, 231, 232, 254, 259, 261, 262]

Natural noxious stimulation

Skin incision

without local anaesthetic

[178]

Chemical injury

e.g. capsaicin, formalin; with or without thermal rekindling

For review[146, 168]

Thermal injury

e.g. heat burn, sunburn/UV

For review [179, 180]

Pharmacological stimulation

Opioid withdrawal (remifentanil) during ongoing IFS or after capsaicin injection

increase in hyperalgesia and allodynia induced by transdermal electrical stimulation or intradermal capsaicin injection on stopping opioid infusion

[188–190]

Opioid withdrawal (morphine and hydromorphone)

acute opioid withdrawal (naloxone) in volunteers made tolerant to opioids

[187]