Intrathecal drug delivery is an effective and safe option for the treatment of chronic pathology refractory to conventional pain therapies. Typical intrathecal administered drugs are opioids, baclofen, local anesthetics and adjuvant medications. Although knowledge about mechanisms of action of intrathecal drugs are every day more clear many doubt remain respect the correct location of intrathecal catheter in order to achieve the best therapeutic result. We analyze the factors that can affect drug distribution within the cerebrospinal fluid. Three categories of variables were identified: drug features, cerebrospinal fluid (CSF) dynamics and patients features. First category includes physicochemical properties and pharmacological features of intrathecal administered drugs with special attention to drug lipophilicity. In the second category, the variables in CSF flow, are considered that can modify the drug distribution within the CSF with special attention to the new theories of liquoral circulation. Last category try to explain inter-individual difference in baclofen response with difference that are specific for each patients such as the anatomical area to treat, patient posture or reaction to inflammatory stimulus. We conclude that a comprehensive evaluation of the patients, including imaging techniques to study the anatomy and physiology of intrathecal environment and CSF dynamics, could become essential in the future to the purpose of optimize the clinical outcome of intrathecal therapy.

Background: Neuromodulation is an effective and reversible treatment option for chronic intractable pain. Spinal cord stimulation (SCS) represents a field of application of neuromodulation and is known to be effective for several conditions including complex regional pain syndrome (CRPS), failed back surgery syndrome (FBSS), and chronic leg and back pain. SCS has some technical limitations that can be bypassed through retrograde neuromodulation. Objective: To examine the safety and efficacy of retrograde neuromodulation in consecutive patients with neuropathic pain in the perineum or lower limb. Study Design: Prospective chart review analyzing one year of retrograde stimulation in our department. Methods: We present a series of 10 patients who underwent retrograde neuromodulation at the University General Hospital of Valencia (Spain). We analyzed the variables that can improve the outcome and help physicians choose retrograde neuromodulation. Results: Seven of 10 patients had an effective treatment and 3 patients had an ineffective stimulation. In the group with the effective treatment the most represented type of pain was radiculopathy and perineal pain. Limitations: This is a prospective, single-center study with a relatively small number of patients and no control group. Conclusion: Retrograde neuromodulation seems to be effective in patients that present with a well localized pain with a clear dermatome distribution. We found retrograde neuromodulation to be effective in radiculopathy related to FBSS. We found it to be limited in the treatment of perineal pain probably due to technical limitations and anatomical reasons besides the lack of knowledge of the etiology of this pain model and the exact mechanisms of action of neuromodulation. Key words: Chronic pain, sp

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