Cortical excitability in tramadol dependent patients: A transcranial magnetic stimulation study.
Addiction to tramadol, a widely used analgesic, is becoming increasingly common. Tramadol can also induce seizures even after a single clinical dose. We tested whether the epileptogenicity of tramadol was associated with any changes in cortical excitability and inhibitory transmission using transcranial magnetic stimulation (TMS).



The study included 16 tramadol dependent patients and 15 age and sex matched healthy volunteers. Clinical evaluation was conducted using an addiction severity index. TMS assessment of excitability was conducted on the motor cortex since the response to each TMS pulse at that site is easily measured in terms of the amplitude of the twitches it evokes in contralateral muscles. Measures included resting and active motor threshold (RMT and AMT respectively), motor evoked potential (MEP) amplitude, cortical silent period (CSP) duration, transcallosal inhibition (TCI), and short interval intracortical inhibition and facilitation (SICI and ICF respectively). Urinary level of tramadol was measured immediately before assessing cortical excitability in each patient.



RMT and AMT were significantly lower, the duration of the CSP was shorter and SICI was reduced in patients compared with the control group. These findings are suggestive of increased neural excitability and reduced GABAergic inhibition following exposure to tramadol. Also there were negative correlations between the severity of tramadol dependence and a number of cortical excitability parameters (AMT, RMT, and CSP with P=0.002, 0.005, and 0.04 respectively).



The results provide evidence for hyperexcitability of the motor cortex coupled with inhibitory deficits in tramadol dependent patients.
Neuropsychiatry Department, Assiut University Hospital, Assiut, Egypt. Electronic address: emankhedr99@yahoo.com.
Eman M
EM
Khedr
Neuropsychiatry Department, Assiut University Hospital, Assiut, Egypt.
Romany H
RH
Gabra
Neuropsychiatry Department, Assiut University Hospital, Assiut, Egypt.
Mostafa
M
Noaman
Neuropsychiatry Department, Assiut University Hospital, Assiut, Egypt.
Noha
N
Abo Elfetoh
Pharmacology Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
Hanan S M
HSM
Farghaly
D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects*; D000071080:Cortical Excitability / Q000187:drug effects* / Q000502:physiology; D019054:Evoked Potentials, Motor / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009293:Opioid-Related Disorders / Q000175:diagnosis / Q000503:physiopathology*; D012146:Rest / Q000502:physiology; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D014147:Tramadol / Q000009:adverse effects*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D055815:Young Adult
D000701:Analgesics, Opioid; D014147:Tramadol
Dependence; Tramadol; Transcallosal inhibition; Transcranial magnetic stimulation