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Another large portion of the plot centers on House's abuse of Vicodin and other drugs to manage pain stemming from an infarction in his quadriceps muscle some years prior, which causes him to walk with a cane. The pain and substance abuse act to increase many of his more objectionable character traits while not impairing his medical acumen, which leads him to often self-medicate.

House is in many respects a medical Sherlock Holmes. This resemblance is evident in various elements of the series' plot, such as House's reliance on psychology to solve a case, House's drug addiction, House's home address, House's playing of an instrument, House's relationship with Dr. James Wilson (a reference to Dr. John Watson), and House's encounter with a crazed gunman credited as "Moriarty", which is the same name as Holmes' nemesis. [5][6]

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