Future Directions in the Management of Pain by Intraspinal Drug Delivery

Abstract

Management of pain by intraspinal delivery of drugs enables physicians to target specific sites of action. While this novel approach is gaining increasing use, well-designed studies are needed. A major limitation is the lack of published information on existing drugs used for intrathecal delivery. (The strengths and weaknesses of this information are reviewed in the accompanying literature review article.) Promising agents such as bupivacaine, hydromorphone, and morphine/clonidine combinations warrant further research in large prospective (ideally randomized and double-blind) clinical safety and efficacy studies. These studies may provide data for pain management guidelines, such as those included in the preceding paper. Research must also address issues of formulation, chemical stability/compatibility, pharmacokinetics, and toxicology during clinical development and drug approval. Finally, more basic studies and early phase trials of other potential agents for intrathecal pain management (e.g., gabapentin) are needed.

Caracterização do complexo de inclusão ropivacaína: beta-ciclodextrina

“…A RVC é um AL semelhante à BVC, possuindo início de ação moderada, longa duração, bloqueio da condução e separação significante entre o bloqueio sensorial e motor 5 . Porém a RVC induz menor toxicidade aos sistemas nervoso central e cardiovascular e promove maior grau de dissociação entre o bloqueio motor e sensorial, sendo útil na administração epidural, infiltração e alívio da dor pós-operatória [6][7][8][9][10][11] . Como as características desejáveis para uma molécula anestésica incluem, além de longa duração de ação e da seletividade para o bloqueio sensorial em relação ao bloqueio motor, a diminuição da toxicidade local e/ou sistêmica 13 , uma alternativa que, atualmente, tem se mostrado capaz de promover estes efeitos desejá-veis é a liberação modificada desses fármacos, através de formação de complexos de inclusão com ciclodextrinas 12,13 .…”

Translational Pain Research: Achievements and Challenges

“…For example, patient-controlled analgesia (PCA), either intravenous or epidural, has provided an effective tool to manage postoperative pain. Introducing PCA into daily clinical practice would not have been possible without extensive preclinical and clinical research on the pharmacology of systemic and spinal analgesics 9, 63, 111, 139, 140, 141. By comparison, clinical management of chronic pain remains difficult, particularly pathological pain such as that from injury to the nervous system.…”

“…As listed in Table 1, new drug delivery systems include, but are not limited to, transdermal, transmucosal, topical, intranasal, and neuraxial (intrathecal/epidural) administration of opioid analgesics, local anesthetics, and non-steroidal anti-inflammatory drugs 9, 27, 28, 50, 63, 89, 109, 111, 112, 114, 139, 140, 141. In many cases, these new drug delivery systems provide more comfort for patients, fewer side effects, and a quicker onset of pain relief than conventional drug delivery methods.…”

Current Developments in Intraspinal Agents for Cancer and Noncancer Pain

“…These guidelines were published in 2000, 2003, and 2007 and were based on “best evidence” and expert opinion, and included guidelines for utilizing an IT drug selection algorithm [2•, 3, 4], the results of surveys given to clinicians in the field [2•], and directives for future studies [5]. …”