1. LA SAPIENZA UNIVERSITY Clinical Neurophysiology of Pain G. CRUCCU, G.D. IANNETTI, A. TRUINI EFNS Panel Neuropathic Pain, Vienna Dept. Neurological Sciences, Rome Clinical Neurophysiology of Pain G. CRUCCU, G.D. IANNETTI, A. TRUINI EFNS Panel Neuropathic Pain, Vienna Dept. Neurological Sciences, Rome

2. 1. Scales and Questionnaires 3. QST (quantitative sensory testing) 4. Neurophysiological Methods 5. Functional Neuroimaging 2. Clinical Examination 6. Biopsy EFNS Guidelines on Pain Assessment (2004)

3. Standard electrodiagnostics Standard neurophysiological tests (NCS, SEP) are useful to demonstrate, quantify and localise a lesion along the sensory pathways cannot assess small-fibre funcion Standard neurophysiological tests (NCS, SEP) are useful to demonstrate, quantify and localise a lesion along the sensory pathways cannot assess small-fibre funcion NCS  SEP 

4. Serra Marchettini Ochoa 1998  Torebjoerk & Ochoa l990  Microneurography Although it has provided important pathophysiological information, microneurography is time consuming and difficult, requiring both an expert investigator and a collaborative patient; hence it is unsuitable for clinical applications (Good Practice Point)

5. the R1 Blink Reflex and the SP1 Masseter Inhibitory Reflex, although non-nociceptive, have great diagnostic value in differentiating Classical from Symptomatic Trigeminal Neuralgia (level A evidence). (Cruccu et al, Neurology 2006) Blink Reflex: Aβ Masseter Inhibitory Reflex: Aβ Trigeminal Reflexes

6. Trigeminal Reflexes in Pain associated to Multiple Sclerosis (Cruccu et al, Pain 2009)

7. Response to treatment and involvement of first trigeminal division are similar in the two populations. Onset age is lower in CTN than STN (P <0.0001). Bilateral neuralgia and sensory deficits only occur in STN (P <0.001). Trigeminal reflexes (TR) are abnormal in STN (87%) and normal in CTN (94%) (P <0.0001). Data from 10 trials (Class I-III) in 628 patients. Differential diagnosis between CTN and STN (from the AAN-EFNS guidelines on trigeminal neuralgia 2008)

8. Cutaneous Silent Period (Truini et al Muscle Nerve 2008) CSPLEP

9. Nociceptive Reflexes Nociceptive reflexes, such as the RIII flexion reflex, the cutanous silent period and the corneal reflex, have little diagnostic value (grade C statement). But the RIII flexion reflex appears to be the most reliable tool in assessing treatment effects (grade B recommendation). (Garcia-Larrea et al, Arch Med Res 2000) Lower limb RIII flexion reflex 

10. Laser Evoked Potentials (LEPs) Laser stimulators raise very quickly the temperature in the superficial layers of the skin, selectively excite free nerve endings (mostly A and C nociceptors) and provide a synchronous afferent volley that is easily recorded from the scalp (over 200 studies have been published, including several top Class)

11. Signals and generators Garcia-Larrea et al 2003 Truini et al 2003

12. LEPs in central neuropathic pain and nonorganic pain Garcia-Larrea et al Brain 2002 In central neuropathic pain (spinal, brainstem, thalamo- cortical) LEPs are suppressed after stimulation of the painful territory, even if the laser pulses evoke hyperalgesia, and may distinguish neuropathic from non- organic pain

13. Spinal pathway conduction of A and C inputs (Iannetti et al J Neurophysiol. 2003)

14. Trigeminal C-LEPs (Cruccu et al, Brain 2003) Because of the short conduction distance and a high receptor density, the trigeminal territory is even more advantageous for eliciting (with low-intensity large-spot pulses) “ultralate” LEPs (N2 latency about 280 ms), mediated by unmyelinated C afferents (conduction velocity 1.2 m/s). highest density of C receptors

15. Trigeminal C LEPs (Cruccu et al, Brain 2003) Patients with trigeminal neuropathy:

16. C-LEPs in patients: Trigeminal Laser evoked potentials in Wallenberg syndrome (Cruccu et al Brain 2003)

17. General results of LEP studies in peripheral neuropathic pain Truini et al NSL 2004

18. Specificity/Sensitivity of LEPs vs. SEPs (Garcia-Larrea and Cruccu, in preparation) Data from 28 studies in 441 patients

19. Pain in Carpal Tunnel Syndrome (Truini et al, Pain 2009)

20. PHN Correl. Pain vs. R1 A-LEP C-LEP responses Significant at least P<0.01 (Truini et al Pain 2008)

21. LEPs assessing response to treatment (Truini et al, Eur J Pain 2009)

22. (Iannetti et al, J Physiol, 2007) CHEPs vs. LEPs 0 1 2 3 4 sec

23. Myelinated-fibre Neuropathy (Truini et al, Pain 2007)

24. Evidence Table LEPs

26. Andrea Truini Giandomenico Iannetti Giorgio Cruccu

27. THANKS FOR YOUR ATTENTION