When managing neuropathic pain in athletes, the choice of treatment must consider not only the effectiveness of the medication but also its potential impact on performance, recovery, and side effects that could interfere with athletic abilities.

1. Anticonvulsants

Anticonvulsants help control the abnormal electrical firing of neurons, which often causes pain from nerve injuries or damage. For athletes, the goal is to manage pain while ensuring that the medication does not impair physical performance, focus, or coordination. These medications achieve this by modulating sodium channels to prevent excessive nerve firing, thus reducing the risk of pain flare-ups during training or competition. They also enhance GABA activity, an inhibitory neurotransmitter, to dampen overactive nerve signals that contribute to persistent pain. Additionally, some anticonvulsants inhibit calcium channels, which can reduce the release of pain-inducing neurotransmitters and improve nerve function without hindering motor skills.

Gabapentin (Neurontin) helps reduce neuropathic pain by blocking excessive nerve activity. It is often used for conditions like radiculopathy as well as peripheral nerve compression. Common side effects include dizziness, sedation, weight gain, and peripheral oedema, which can impact stamina, concentration, and mobility. Gabapentin typically starts at 300 mg once daily or in divided doses. The dose is gradually increased to 900–1800 mg per day, divided into two to three doses, based on efficacy and tolerance. The maximum dose is usually 3600 mg/day. Athletes should start with a lower dose and gradually increase it to minimize sedation or dizziness, which can impact performance. It is important for athletes to monitor their response to the medication to ensure it does not interfere with training or competition.

Pregabalin (Lyrica) works similarly to gabapentin by binding to the α2δ subunit of calcium channels but has a more potent effect and faster onset [8]. It is effective for conditions like fibromyalgia, which athletes may experience from overuse or long-term strain. Pregabalin is usually taken in divided doses twice a day, with adjustments based on individual response. Side effects include sedation, dizziness, weight gain, and peripheral edema, which can interfere with muscle recovery, endurance, and agility. While pregabalin’s fast onset can offer quick pain relief, athletes should monitor its impact on performance during training or competition. Pregabalin typically starts at 75 mg twice daily. The dose can be increased to 150–300 mg per day, divided into two doses. The maximum dose is usually 600 mg/day, also divided into two doses. Pregabalin works quickly, and higher doses may offer faster relief, but athletes should be cautious about sedation and dizziness, which can affect reaction time and coordination. It is important to start with a lower dose and adjust as needed to minimize these effects.

Carbamazepine (Tegretol) works by stabilizing sodium channels to prevent the over-firing of nerves, making it effective for pain caused by nerve compression or irritation [9]. It is commonly used to treat conditions like trigeminal neuralgia, which may occur in athletes after facial injuries, and other neuropathic pain due to direct nerve trauma [10]. The drug is typically started at a low dose and gradually increased, with regular monitoring to check for potential side effects and drug interactions. Common side effects include dizziness, drowsiness, nausea, and rash, while more serious issues like liver toxicity and blood disorders require routine testing. Carbamazepine typically starts at 200 mg twice daily. The dose is increased by 200 mg every two to three days until reaching 800–1200 mg per day, usually divided into two doses. The maximum dose is typically 1600 mg/day, though some cases may go up to 2000 mg/day with caution. Carbamazepine is effective for nerve compression-related pain but can cause sedation and cognitive dulling, which may affect mental sharpness and reaction times.

Carbamazepine, lamotrigine, and topiramate are used less frequently in the treatment of neuropathic pain compared to gabapentin and pregabalin [11, 12]. While they can be effective for specific types of neuropathic pain, such as trigeminal neuralgia or neuropathies related to compression (in the case of carbamazepine), they tend to have a more complex side effect profile. These medications are also less well tolerated by athletes due to potential impacts on mental clarity, cognitive function, and coordination, which can interfere with training and competition. Therefore, they are generally considered second or third-line options, often prescribed when first-line treatments (gabapentin or pregabalin) do not provide adequate relief (Table 1).

• 2.Antidepressants

Tricyclic Antidepressants (TCAs) are one of the most widely used classes of medications for managing neuropathic pain, particularly when other first-line treatments (e.g., anticonvulsants) are not effective or well-tolerated. TCAs work primarily by inhibiting the reuptake of serotonin and norepinephrine in the central nervous system. This action increases the levels of these neurotransmitters in the synaptic cleft, enhancing their effects on pain modulation pathways. Specifically, the serotonin-norepinephrine balance plays a key role in controlling pain signals transmitted via the spinal cord and the brain.

Amitriptyline (Elavil) is commonly used when athletes experience nerve compression, radiculopathy, or post-surgical pain after orthopedic procedures like ACL reconstruction [13, 14]. The initial dose usually starts at 10–25 mg at bedtime, with gradual increases based on tolerance and response. The therapeutic dose typically ranges from 50 to 150 mg per day.

Nortriptyline (Aventyl) is used for chronic pain management in athletes, particularly for conditions like CRPS, tendinopathy, or persistent pain after fractures. The starting dose is typically 25 mg before bed, with the therapeutic dose usually ranging between 50 and 100 mg per day [15].

SNRIs (Selective Serotonin-Norepinephrine Reuptake Inhibitors), such as Duloxetine and Venlafaxine, are effective for treating neuropathic pain in athletes, particularly when there is co-occurring depression or anxiety often resulting from chronic injuries or overuse [16, 17]. For Duloxetine, the starting dose is 30–60 mg per day (once daily), with an effective dose typically ranging from 60 to 120 mg per day, which can be increased based on tolerance. For Venlafaxine, the starting dose is 37.5–75 mg per day (divided dose), with an effective dose between 75 and 225 mg per day (divided into two doses), adjusted for side effects [18]. SNRIs help athletes by providing pain relief for chronic musculoskeletal pain, sciatica, fibromyalgia, and nerve pain while also enhancing mood, reducing anxiety, and aiding in stress management during recovery [19, 20]. They work by increasing serotonin and norepinephrine, which helps with both pain modulation and mood regulation. Athletes should be cautious of dizziness or nausea, which may interfere with training, and monitor blood pressure, especially for those in strength-based sports where elevated blood pressure could be a concern (Table 2).

• 3.Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs work by inhibiting COX-1 and COX-2 enzymes to reduce inflammation and pain, but they are not the first-line treatment for neuropathic pain, which involves nerve injury and central sensitization. Non-selective NSAIDs (e.g., Ibuprofen, Naproxen) may help with inflammation from conditions like radiculopathy or entrapment neuropathies in athletes, but they are less effective for the burning or shooting pain typical of nerve damage. COX-2 selective NSAIDs (e.g., Celecoxib, Etoricoxib) may be used for inflammation in cases like nerve root inflammation, offering fewer gastrointestinal side effects, but they are still limited to addressing the inflammatory component and not the neuropathic pain itself. Table 3 provides an overview of various NSAIDs, their dosages, and corresponding indications.

• 4.Topical Agents

Topical agents are an important class of treatments for managing neuropathic pain in athletes, especially when the pain is localized or if there is a need to avoid systemic side effects associated with oral medications. They are often used for conditions like localized nerve entrapment, post-surgical pain, or peripheral neuropathy.

Lidocaine patches are local anaesthetics that block sodium channels, providing targeted pain relief by preventing pain signal propagation along nerves [21]. They are primarily used for neuropathic pain from conditions like carpal tunnel syndrome and localized musculoskeletal pain from nerve compression or injury [22]. Applied directly to the painful area for 12 h, the patches are simple, non-invasive, and can be cut to fit the affected area. Side effects are minimal, mainly skin irritation. They are ideal for patients sensitive to systemic medications, though their effectiveness is limited to superficial, localized pain and not suitable for deep or widespread nerve pain.

Capsaicin, derived from chili peppers, depletes substance P, a neuropeptide involved in pain transmission, leading to reduced pain signaling over time [23]. High-concentration patches (8%) are applied in clinical settings for conditions like postherpetic neuralgia, diabetic neuropathy, osteoarthritis with neuropathic components, CRPS, and localized neuropathic pain [24, 25]. The patch is applied for 60 min, with effects lasting for months. Side effects include burning sensations and skin irritation, but systemic effects are minimal. Capsaicin offers long-term pain relief and reduces reliance on oral medications, making it beneficial for athletes, though its initial discomfort may deter consistent use.

Diclofenac, a topical NSAID, inhibits COX enzymes to reduce prostaglandin production, providing localized pain relief and reducing inflammation [26]. It is effective for osteoarthritis-related pain, soft tissue injuries, tendinitis, bursitis, and acute sports injuries [27]. Available as a gel or patch, it is applied three to four times daily directly to the painful area. Side effects are minimal and include skin irritation or photosensitivity. Topical application minimizes systemic side effects compared to oral NSAIDs, though it may be less effective for deep tissue pain and should not be used on open wounds. Consistent use is necessary for optimal relief.

• 5.Corticosteroid injections

Corticosteroid injections are a targeted and effective treatment for managing neuropathic pain in athletes, especially when caused by nerve compression, inflammation, or irritation. These injections work by reducing swelling, suppressing immune-mediated nerve damage, and lowering the sensitivity of pain-sensing nerve.fibres Common conditions treated include carpal tunnel syndrome, where the injection is administered into the carpal tunnel to alleviate pressure on the median nerve, and tarsal tunnel syndrome, where it targets the tibial nerve near the medial ankle. In cases such as ulnar nerve entrapment, injections are applied around the cubital tunnel at the elbow, while for sciatica, they are directed to the epidural space or piriformis muscle. For Morton’s neuroma, injections are placed into the intermetatarsal space, and in post-surgical nerve pain, they are applied near the surgical site to address persistent inflammation [28]. Chronic regional pain syndrome may require regional or epidural injections for relief [29]. Medications commonly used include corticosteroids such as methylprednisolone, triamcinolone, or dexamethasone, providing effects that last around four to six weeks, often combined with local anaesthetics like lidocaine or bupivacaine for immediate, short-term relief. While corticosteroid injections offer localized, potent relief with minimal systemic side effects, they are most effective when combined with physical therapy and efforts to address the underlying cause of the pain.

• 6.Opioids

Opioids are powerful medications commonly used for managing severe pain, including neuropathic pain, especially when other treatments such as NSAIDs, anticonvulsants, or antidepressants are ineffective [30, 31]. Despite their effectiveness in pain relief, opioids come with a high potential for dependence, tolerance, and various other significant side effects. As a result, they are typically reserved as a last-resort option for short-term use in neuropathic pain and are carefully monitored when prescribed to minimize the risks associated with long-term use.

Opioids work by binding to opioid receptors in both the central nervous system and peripheral nervous system. These receptors include mu, kappa, and delta receptors. Mu receptors are primarily responsible for pain relief, but also contribute to euphoria, respiratory depression, and the potential for addiction. Kappa receptors also provide analgesia but are associated with dysphoria and hallucinations. Delta receptors play a lesser role in pain relief but help modulate pain. By binding to these receptors, opioids block pain signal transmission and alter the emotional response to pain, providing relief but also carrying a risk of dependence and other side effects. Table 4 represents the information on common opioids used for neuropathic pain.

Short-term opioid use in athletes is indicated for severe acute pain (e.g., post-surgery, flare-ups of neuropathic conditions) and breakthrough pain that does not respond to other treatments. Opioids should be prescribed for the shortest duration possible, typically three to seven days, to manage acute pain. Combining opioids with non-opioid therapies, such as NSAIDs, anticonvulsants (e.g., gabapentin), or physical therapy, can help minimize reliance on opioids. Additionally, adjunct medications like laxatives for constipation and anti-nausea drugs can manage common side effects. It is crucial to maintain clear documentation of the need for opioids, prescribed dosages, and any refills. Regular follow-up appointments are essential to monitor the patient’s progress and assess the risk of misuse.